Dm hund
Hvad er MDR1 og DM
MDR1 og DM er to sygdomme som pt. er meget oppe at vende i hundeverden, da der er fundet flere hunde som har vist sig at vжre bжrer af en af disse sygdomme. Flere og flere opdrжttere er begyndt at teste, selvom det ikke er et krav her i Danmark at man tester sine avlsdyrs for disse sygdomme, men opdrжtterne har gjort det for at fе mere viden om hvad deres avlsdyr gemmer pе. Teknologien har gjort det muligt at lave nye gentest pе forskellige arvelige og racerelevante sygdomme.
MDR1 og DM er som sagt to sygdomme, som har vist sig at findes i flere af vores avlsdyr, heldigvis ikke i sе mange her hjemme i Danmark, men flere i udlandet har vist sig at vжre bжrer eller i vжrste fald syge. Derfor mener jeg bestemt, det er vжrd at kigge nжrmere pе disse to sygdomme og ikke mindst teste vores avlsdyr, for at undgе at det skal blive et problem her i Danmark.
Disse sygdomme er selvfшlgelig ogsе relevante for den helt almindelige hundeejer at vide noget om, da det kan have betydning for den hund som lever en stille og roligt familieliv.
Hvis en hund har denne genfejl, mutation pе MDR1 genet, betyder det, at den berшrte hund kan blive alvorlig syg af visse medicinske prжparater. Mutationen gшr blodhjernebarriereren ”utжt”, sе stoffet fшres over denne barrier i stшrre mжngder end ved hunde som ikke bжrer denne mutation. Stoffet kan derefter ikke pumpes korrekt ud igen og der kan derved ske en ophobning og risikoen for bivirkninger шges.
Nogle af de medicinske prжparater som kan have betydning, findes i blandt andet loppemidler og ormemidler, som vi ofte bruger i dagligdagen. Derfor er der god grund til at vide om ens hund har en mutation pе MDR1-genet (Multi Drug Resistance), da det kan betyde, at hunden kan blive alvorlig syg.
Denne mutation findes hos flere forskellige hyrdehunderacer, derfor kan det vжre en god ide at man er opmжrksom pе dette, nеr man er ejer af en hyrdehunderace uanset om man шnsker at bruge hunden i avl eller ej. (Findes ogsе i andre racer, sеsom collie-racer og mynde-racer).
Nеr man lжser pе nettet og i bшger om denne sygdom, er forskerne desvжrre ikke helt enige om hvornеr en hund bliver overfшlsom for de enkelte lжgemidler.
Nogle af forskerne mener, at en bжrer (MDR1 +/-) kan vжre overfшlsom, mens andre siger at det kun er de hunde, som er syge (MDR1 -/-) der kan vжre overfшlsomme.
Denne uenighed blandt forskerne er et udtryk for at man ikke har belyst omrеdet fuldt ud endnu, da der stadig er en usikkerhed pе nogle omrеder som fx hvornеr en hund bliver berшrt af mutationen. Men det er forventeligt at der i de kommende еr vil komme mere prжcise retningslinjer, jo mere der forskes i det.
Og hvordan skal vi som avlere og hundeejere, sе forholde os til dette?
Ja det er jo et svжrt spшrgsmеl, eftersom forskerne ikke er enige. Men jeg mener, at hvis man som hundeejer af en hyrdehund tager sine forholdsregler, og sе vidt muligt gеr uden om de prжparater, som findes pе listen, sе gшr vi hvad vi kan for at passe pе vores hunde.
Og jo flere hunde der bliver testet, jo mere vil det ogsе give et overblik over hvor udbredt denne mutation er.
For at teste om ens hund har denne mutation, kan man tage til egen dyrlжge, som udtager en blodprшve og sender denne ind til et laboratorium.
Testen kan ogsе udfшres ved hjжlpe af en mundsvaber, dog er en blodprшve at anbefale, da man pе den mеde sikre at der kommer nok brugbart DNA materiale med til laboratoriet at teste pе.
Arvegangen for MDR1
Hvis hunden er fri, vil det vжre skrevet sеledes: MDR1 +/+ (Man kan ogsе se det skrevet som MDR1 N/N)
Hvis hunden er bжrer, vil det vжre skrevet sеledes: MDR1 +/- (Man kan ogsе se det skrevet som MDR1 N/A)
Hvis hunden har sygdommen, vil det vжre skrevet sеledes: MDR1 -/- (Man kan ogsе se det skrevet som MDR1 A/A)
Genotypen kan vжre skrevet pе forskellige mеder, dog er de ovenstеende mеder de mest brugte.
N stеr for Not affected (ikke pеvirket)
A stеr for Affected (pеvirket)
At man har en hund, som er bжrer, betyder ikke nшdvendigvis at denne bшr udelukkes fra avlen, men det betyder blot, at denne kun bшr parres med hunde som er fri af sygdommen. Det samme gжlder i princippet, hvis man har en hund, som har sygdommen.
Hvalpen fеr et gen fra sin mor og et gen fra sin far.
Hvis moderens genotype er MDR1 +/+ vil hun kun kunne give et + videre til sin hvalp, hvis faderens genotype er MDR1 +/- vil han kunne give enten et + eller et - videre til hvalpen.
Sе en parring mellem disse to hunde vil give 50 % hvalpe med genotypen MDR1 +/+ og 50 % med genotypen MDR1 +/-
Altsе kan vi konkluderer, at der aldrig vil kunne komme syge hunde ud af denne kombination.
Men derimod vil man kunne fе syge hunde, hvis man bruger to bжrere sammen. Her vil 25 % blive syge, 25 % blive fri og 50 % blive bжrer.
En parring mellem en fri (MDR1 +/+) og en bжrer (MDR1 +/-)
Som skrevet halvdelen bliver fri (MDR1 +/+) og halvdelen bliver bжrer(MDR1 +/-).
En parring mellem en bжrer (MDR1 +/-) og en bжrer (MDR1 +/-)
Her vil 25 % af hvalpene blive syge (MDR1 -/-), 25 % bliver fri (MDR1 +/+) og 50 % bliver bжrer (MDR1 +/-)
En parring mellem en rask (MDR1 +/+) og en syg (MDR1 -/-)
Alle disse hunde vil blive bжrer men ingen af dem vil blive syge.
Liste over medicinske prжparater, som har indflydelse pе hunde med mutation pе MDR1-genet
Mange forskellige medicinske prжparater og grupper af disse er blevet rapporteret at forеrsage problemer hos hyrdehunderace, der bжrer MDR1 mutation.
Fшlgende lжgemidler er blevet dokumenteret at forеrsage problemer hos hunde med MDR1-mutationen:
§ Acepromazine ( beroligende og prж-bedшvelsesmiddel)
§ Butorphanol ( analgetisk og prж-anжstetisk middel)
§ Emodepside (findes i profender, som er en ormekur)
§ Erythromycin. ( Erythromycin kan forеrsage neurologiske tegn hos hunde med MDR1 mutation.)
§ Ivermectin (antiparasitisk middel)
§ Loperamide ( Imodium – bruges til hunde med diarre)
§ Selamectin , milbemycin, and moxidectin ( antiparasitisk middel - svarende til ivermectin)
§ Vincristine, Vinblastine, Doxorubicin (kemoterapeutisk lжgemiddel)
Der er mange andre lжgemidler, som har vist sig at blive pеvirker af det protein, der kodes af MDR1-genet hos mennesker, men der foreligger endnu ikke data med hensyn til deres virkning pе hunde med MDR1-mutationen.
DM menes at vжre en autoimmun sygdom, det vil sige at det er kroppens eget immunsystem, der angriber hundens egne organer. I dette tilfжlde myelinskederne, som ligger rundt om nervetrеdene i rygsшjlen. Sygdommen ses fшrst i udbrud fra hunden er +7 еr gammel. Den pеrшrte hund vil langsom miste evnen til at bevжge sig, og man vil se delvis eller fuldstжndig lammelse i hundens bagkrop, selve udviklingen af sygdommen kan tage fra 6-12 mdr. Det fшrste tegn pе sygdommen er tab af koordination eller muskel kontrol i bagbenene. Ofte bliver hunden slingrer i bagpartiet, slжber tжerne henover jorden, man ser ogsе nogle hunde krydser bagbenene over hinanden nеr de gеr.
Denne lidelse er ikke smertefuld for hunden, men derfor bшr den stadig tages alvorligt, eftersom det oftest ender i en aflivning, da hunden ikke vil kunne bruge sine bagben, den vil oftest miste kontrollen over afsжtning af urin og fжces.
Dette skyldes en mutation, som gшr at rygmarven bliver gradvist nedbrudt. Mutationen forеrsager en fejl i signalerne fra hjernen til bagparten.
Forskerne mener ikke nшdvendigvis, at hunden udvikler DM selvom den har denne mutation (DM DM/DM), da man mener der skal andre faktorer til for at udviklingen finder sted. Forskning pе dette omrеde er stadig meget ny og man derfor ikke helt kortlжgge, hvad der skal til for at en hund udvikler DM.
Arvegangen for DM
Man snakker om, at hunden kan vжre fri, bжrer eller at den har sygdommen.
Hvis hunden er fri, vil det vжre skrevet sеledes: DM N/N
Hvis hunden er bжrer, vil det vжre skrevet sеledes: DM N/DM (Man kan ogsе se det skrevet DM N/A)
Hvis hunden har sygdommen, vil det vжre skrevet sеledes: DM DM/DM (Man kan ogsе se det skrevet som A/A)
N stеr for Not affected (ikke pеvirket)
A stеr for Affected (pеvirket)
At man har en hund som er bжrer, betyder ikke nшdvendigvis, at denne bшr udelukkes fra avlen, men det betyder blot, at denne kun bшr parres med hunde, som er fri af sygdommen. Det samme gжlder i princippet, hvis man har en hund, som har sygdommen.
Hvalpen fеr et gen fra sin mor og et gen fra sin far.
Hvis moderen har DM N/N vil hun kun kunne give et N videre til sin hvalp, hvis faderen hedder DM N/DM vil han kunne give enten et N eller et DM videre til hvalpen.
Sе en parring mellem disse to hunde vil give 50 % hvalpe med genotypen DM N/N og 50 % med genotypen DM N/DM
Altsе kan vi konkludere, at der aldrig vil kunne komme syge hunde ud af denne kombination.
Men derimod vil man kunne fе syge hunde, hvis man bruger to bжrer sammen. Her vil 25 % blive syge, 25 % blive fri og 50 % blive bжrer.
En parring mellem en fri (DM N/N) og en bжrer (DM N/DM)
Som skrevet halvdelen bliver fri (DM N/N) og halvdelen bliver bжrer(DM N/DM).
En parring mellem en bжrer (DM N/DM) og en bжrer (DM N/DM)
Her vil 25 % af hvalpene blive syge (DM DM/DM), 25 % vil blive fri (DM N/N) og 50 % vil blive bжrer (DM N/DM)
En parring mellem en rask (DM N/N) og en syg (DM DM/DM)
Alle disse hunde vil blive bжrer men ingen af dem vil blive syge.
Skrevet af Aut. Veterinжrsygeplejerske og udd. Hundetrжner Betina Vestergaard
Canine Degenerative Myelopathy DM Test Code 355
For Breeds*: American Eskimo Dog, Bernese Mountain Dog**, Borzoi, Boxer, Cardigan Welsh Corgi, Chesapeake Bay Retriever, German Shepherd dog, Golden Retriever, Great Pyrenees, Kerry Blue Terrier, Pembroke Welsh Corgi, Poodle (all varieties), Pug, Rhodesian Ridgeback, Shetland Sheepdog, Soft Coated Wheaten Terrier, Wire Fox Terrier
*These are breeds for which there is evidence of a strong correlation between the SOD1 mutation and clinical symptoms of Degenerative Myelopathy (DM). Upon request from the owner, OptiGen will perform the DM test for any breed NOT listed here.
**Two different mutations in the SOD1 gene can cause Degenerative Myelopathy in Bernese Mountain Dogs (BMD). A test for the second mutation, called DM-BMD, is expected to be available at OptiGen for BMDs in the near future.
Clinical signs/Disease Description:
Canine Degenerative Myelopathy (DM) has been recognized for more than 35 years as a spontaneously occurring spinal cord disorder in older dogs, with age of onset ranging between 8 and 14 years. Initially thought to be specific to German Shepherds, DM has been diagnosed in many other breeds, being most prevalent in Pembroke Welsh Corgis, Boxers, Rhodesian Ridgebacks and Chesapeake Bay Retrievers.
Degenerative Myelopathy is characterized by a gradual degeneration of spinal reflexes and muscle weakness. The initial signs of DM typically include loss of coordination (asymmetric ataxia) in the hind limbs. The symptoms worsen with time when the affected dog can no longer support its weight in the hind limbs. The age of onset and the speed of disease progression is variable. Affected small breed dogs often develop DM at an older age and deteriorate more slowly than affected dogs of large breeds. Affected medium to large breed dogs can be difficult to manage and owners often elect euthanasia when their dog can no longer support weight in the hind limbs.
For owners and veterinarians it is important to make a distinction between progressive Degenerative Myelopathy and a variety of acquired compressive spinal cord diseases and injuries because the initial symptoms are similar but the outcome and the approach for treatment is very different.
DM Mutation Test:
The DNA-based DM test allows to determine the genotype of a tested dog with respect to the SOD1 mutation as being:
Homozygous Normal - this dog has two copies of the normal gene and is likely to be free of the DM disease.
Carrier - this dog has one copy of the mutation and one copy of the normal gene. The chances that the dog will develop the disease are low.
Homozygous Affected - this dog has two copies of the mutated SOD1 gene and has a high risk of developing the disease during its lifetime.
The mode of inheritance of the SOD1 mutation is best described as autosomal recessive, meaning that dogs of both sexes have a much higher risk of developing the disease when they receive two copies of the mutated gene, one from each parent. For detailed recommendations on breeding strategies using results of OptiGen testing, please, refer to the Breeding Strategy Chart below.
This table highlights in yellow the breedings that will NOT produce DM-affected pups due to the presence of the SO D1 mutation, which is the major risk factor associated with the disease. These breedings include at least one parent proven "Normal/Clear" by the OptiGen DM test. All other combinations are at risk of producing DM-affected pups.
- Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 106(8):2794-9.
- Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med. 2014 Feb 13. doi: 10.1111/jvim.12317.
Well-being is common sense
DM, Degenerativ Myelopati
DM står for Degenerativ Myelopati.
DM menes at være en autoimmun sygdom, det vil sige at det er kroppens eget immunsystem, der angriber hundens egne organer. I dette tilfælde myelinskederne, som ligger rundt om nervetrådene i rygsøjlen. Sygdommen ses først i udbrud fra hunden er +7 år gammel. Den pårørte hund vil langsom miste evnen til at bevæge sig, og man vil se delvis eller fuldstændig lammelse i hundens bagkrop, selve udviklingen af sygdommen kan tage fra 6-12 mdr. Det første tegn på sygdommen er tab af koordination eller muskel kontrol i bagbenene. Ofte bliver hunden slingrer i bagpartiet, slæber tæerne henover jorden, man ser også nogle hunde krydser bagbenene over hinanden når de går.
Denne lidelse er ikke smertefuld for hunden, men derfor bør den stadig tages alvorligt, eftersom det oftest ender i en aflivning, da hunden ikke vil kunne bruge sine bagben, den vil oftest miste kontrollen over afsætning af urin og fæces.
Dette skyldes en mutation, som gør at rygmarven bliver gradvist nedbrudt. Mutationen forårsager en fejl i signalerne fra hjernen til bagparten.
DM Exon 1 og DM Exon 2
Der kendes nu 2 mutationer** for DM, både en på Exon 1 og Exon 2, disse vil oftest benævnes DM Exon 1 og DM Exon 2.
DM Exon 2 er den vi tidligere har kendt, og som vi indtil nu har fået testet for hos bl.a. Ofa, Antagene, DDC o.l.
Den kan finde mutation for DM hos mange racer.
Det er kun hos Berner Sennen det har været muligt, at spore DM Exon 1.
Vil vi have klarhed over, om vore hunde er clear/carrier/at risk for DM skal vi teste for begge.
*exon er dele af et gen, der anvendes til kode for proteinsyntesen i en celle.
**mutation er en ændring i en celles arvemateriale (DNA).
DM Exon 2: Clear: 49% Carrier: 39% Affected: 12%
Prisen for denne test hos Laboklin er pr. 02.01.2015 ca 418,00 dk.kr + evt. konsultation og håndtering af prøven.
2. G enomisk avlsværdi albue dysplasi
3. G enomisk avlsværdi hofteledsdysplasi
4. Undersøgelse af degenerative myelopati exon 1 og exon 2
5. SSV prætest på histiocytisk sarkom
(DBSK´s Avls- og Sundhedsudvalg yder tilskud på halvdelen til hunde som blev anbefalet til avl ved klubbens avlsbeskrivelse).
Arvegangen af DM
Hvis hunden er fri, vil det være skrevet således: N/N (DM N/N) normal/fri
Hvis hunden er bærer, vil det være skrevet således: A/N (DM N/DM) carrier/bærer
Hvis hunden har sygdommen, vil det være skrevet således: A/A (DM DM/DM) at risk/syg
A står for Affected (påvirket)
Så en parring mellem disse to hunde vil give 50 % hvalpe med genotypen N/N (DM N/N) normal/fri og 50 % med genotypen A/N (DM N/DM) carrier/bærer
Altså kan vi konkludere, at der aldrig vil kunne komme syge hunde ud af denne kombination.
En parring mellem A: normal/fri (eks. din tæve) og B: Carrier/bærer (eks. min Oliver)
En parring mellem A: carrier/bærer (eks. din tæve) og B: carrier/bærer (eks. min Oliver)
En parring mellem A: at risk/ syg og B: normal/fri
Forslag til valg af laboratorier som foretager test for DM
- Via deres hjemmeside bestiller du kit til at udføre testen på. Derved bliver du også oprettet i deres system, og kan følge "din sag". En kit er en svab, som foretages i kinden på hunden.
- Når du modtager kitten, kan du selv foretage testen. Personligt har jeg valgt, at lade min dyrlæge foretagen testen, når jeg alligevel en aftale hos ham. Han tjekkede chipnummer og bekræftede over Offa, at det er den korrekt hund som passer til testen.
- I Athos´s tilfælde blev han testet den 31. okt. 2013 og svaret var tilgængelig den 26. nov. 2013. Du kan se Athos´s resultat her. Der går nu herefter nogle ugerne inden du pr post vil modtage et dokument på resultatet på testen.
- Blodprøve.
- Buccal som bruges til at foretage en svab-test i kinden. Disse kan bestilles på deres hjemmeside. Bestilling af buccal.
- Ulveklør. Du kan enten anvende ulvekloen til testen. Du skal blot indsende den hele ulvekloen, efter at den er blevet fjernet. Det er vigtigt ikke at placere prøven i en plastikpose. Brug venligst et papir kuvert. Dette vil forhindre forfald og nedbrydning af prøven under opbevaring og forsendelse. Ulvekløer prøver bør sendes inden for et par dage. En anden mulighed er at samle en lille blodprøve fra det område, hvor ulvekloen blev fjernet. Dette gøres ved at duppe området, hvor kloen blev fjernet med spidsen af en vatpind og opsamling af en lille mængde blod. Prøverne anbringes i et papir kuvert og skal have lov at tørre i 15-30 minutter før forsegling.
- Buccal som bruges til at foretage en svab-test i kinden. Disse kan bestilles på deres hjemmeside. Bestilling af buccal.
- Testen kan foretages hjemme, og på hunde i alle aldre.
Eksempel på en buccal
Min personlige holdning til test for DM
- 40% er N/N (DM N/N) normal/fri, i alt 984 af 2434
- 49% er A/N (DM N/DM) carrier/bærer, i alt 1181 af 2434
- 11% er A/A (DM DM/DM) at risk/syg, i alt 269 af 2434
Og holder man denne statistik op med: "Degenerative myelopati er en neurologisk lidelse, der påvirker rygmarven og forårsager neurologiske symptomer som svært ved at koordinere bevægelser i bagbenene, bagbenssvaghed og sensorisk tab. Symptomerne er progressiv, men ikke forbundet med smerte. De fleste hunde, der udvikler sygdommen er ældre end 8 år. I øjeblikket er der ingen behandling eller helbredelse. Den kliniske diagnose bekræftes af dyrlægen gøre tests for at udelukke andre årsager til symptomerne. Den eneste måde at vide med sikkerhed, er at undersøge rygmarven efter døden, og se efter sygdomsspecifikke ændringer", bør vi måske lige overveje vores holdning til DM endnu engang.
Dm hund
DM eller Canine degenerative myelopati
Hvad er Canine Degenerative Myelopati (DM)?
Er en langsomt fremadskridende, neurologisk sygdom der medfører ødelæggelse af myelin (nerve kappen) i rygmarven. Sygdommen medfører bevægelsesforstyrrelser – ramte hunde udvikler gradvis ukoordinerede bevægelser i bagparten, og fører over tid til lammelse, den er ikke smertefuld og udvikler sig hos de racer hvori den er mest kendt fra 7-8 års alderen.
I øjeblikket har vi meget få kliniske data om DM syge Ridgebacks. . I USA er der ifølge RRCUS (den amerikanskre RR klub) sundhedsundersøgelse i fem års perioden fra 1986 til 1991, ni dokumenterede tilfælde – en relativt lav forekomst når man ser på den samlede population af Ridgebacks i USA. I perioden 2005 og 2006 blev fire tilfælde bekræftet. Men RRCUS påpeger også at diagnosen af denne sygdom er ikke let, og der er derfor formentlig flere hunde lider under DM.
Forskning i sygdommen
Der finden en DNA test for DM, et amerikansk-svensk forskerteam for nyligt har fundet ud af at hunde (Welsh Corgi) med en mutation af SOD1 genet på begge alleler i DNA’et har en større sandsynlighed for at udvikle sygdommen. Dog mener de, at der hos andre racer f.eks. Howavart også kræves andre gener før sygdommen udvikles.
Dette betyder at selvom genet SOD1 er en risikofaktor, er det ikke det gen alene der fører til sygdommens udbrud!
Ifølge professor Tosso Leeb, som forsker i sygdommen på Institut for Genetik i Bern (i samarbejde med Uppsala Universitet), kan man antage, at dette også gælder for Rhodesian Ridgeback og han mener at modifikater genet bør findes før man går videre.
Faktisk er udviklingen af den diagnostiske procedure stoppet og arbejdskraft og donationer af penge bruges nu til at indsamle blodprøver. Prof. Leeb har pt omkring 20 blodprøver fra diagnosticerede DM hunde, men han skal minimum bruge omkring 50 . Han vil også gerne have Rhodesian Ridgeback med i undersøgelsen, og har derfor brug for blodprøver fra ramte hunde med en klar DM diagnose. Der er så vidt vides ikke diagnosticeret Rhodesian Ridgebacks med DM i Europa, de få sikkert diagnosticerede RR’s i USA har alle været ældre hunde (over ni år ofte en hel del ældre) og da diagnosen er mere et spørgsmål om at udelukke andre sygdomme er den langt fra simpel og der kan være flere fejldiagnosticerede hunde.
I tvivlstilfælde er der dog også mulighed for at DNA teste for mutation af SOD1 genet.
Lidt om genetikken :
Her er en kort forklaring af de tre genotyper (Kilde: Laboklin):
Genotype N / N – homozygot [homozygote] sundt
Denne hund er ikke bærer mutationen, og har en ekstremt lav risiko for at få
Genotype N / DM – heterozygot [heterozygot] bærer
Denne hund bærer en kopi af det muterede gen. Den har en ekstremt lavt risiko for at få DM, men kan give mutationen til ca 50% af sit afkom. Sådan en hund bør kun parres med en DM mutationen-fri hund
Genotype DM / DM – homozygot (risiko) [homozygote]
Denne hund bærer to kopier af det muterede gen, og har en ekstremt høj risiko for at udvikle DM. Den vil give mutationen til alle sine afkom og bør kun parres til en ”fri” hund
Amerikansk Undersøgelse
OFA (Orthopedic Foundation for Animals) foretager i øjeblikket en større undersøgelse om udbredelsen af DM, indtil videre er 1425 Ridgebacks blevet DNA testet, og racen er derfor den mest undersøgte af alle racer.
DNA testen er kun for mutationen af SOD1 genet og der er ingen oplysninger om nogen af hundene er diagnosticerede. Dog har denne undersøgelse allerede haft en stor indflydelse på Ridgeback avlen i USA, ikke alene har enkelte opdrættere valgt at trække deres hunde ud af avlen efter de er blevet identificeret som bærere, hvilket er stik imod OFAs anbefalinger der blot går ud på at man bør tage hensyn til det i avlen (dvs at bærer skal parres med fri). Hvis alle bærere udelukkes fra avlen vil vi miste 40% af vores gen materiale med et slag. Og hvad så med den næste test? Og den næste?
Med de efterhånden mange, mere eller mindre relevante, gentests der er tilgængelige kan vi som opdrættere meget let gå hen og miste den genetiske mangfoldighed som vi har arbejdet så mange år på at udbygge.
Bør man så overhovedet teste sine avlsdyr? Tjohh, Det er vigtigere end nogensinde at vide om der ”er” noget i linjerne: hvis f.eks. din hunds bedstefar er blevet diagnosticeret med DM – eller, har givet hunde med DM, eller evt. er i risiko gruppen, jo så er det en god ide at teste. Og hvis det så viser sig at hunden er bærer skal man selvfølgeligt sørge for at dens avlspartner ikke er.
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Poster publiceret af Admin, er skrevet af mig, Helle. Jeg har brændt for Rhodesian Ridgebacks siden jeg forelskede mig i et billede in en hundebog da jeg var 10. Vi var så heldige at få vores første Ridgeback i begyndelsen af 90'erne da hele familien boede i Zambia og siden har der altid været store brune hunde i familien
Degenerative Myelopathy and
the Cavalier King Charles Spaniel
Symptoms
- Diagnosis
- DNA Testing
- Treatment
- Breeders' Responsibilities
- What You Can Do
- Research News
- Related Links
- Veterinary Resources
Canine degenerative myelopathy (CDM or DM) * is a crippling and ultimately fatal neurological disease of the spinal cord, the symptoms of which begin to occur around age 8 years or older in most patients. "Myelopathy" refers to a disease of the spinal cord. "Degenerative" means progressive.
Degenerative myelopathy is a chronic and progressive disorder which cannot be cured and results in lameness and eventual paralysis of the hind legs, followed by further muscle control deterioration. The disease affects the T3 to L3 segments of the spinal cord. It is considered to be the canine equivalent to amyotrophic lateral sclerosis (ALS -- Lou Gehrig’s disease) in humans.
CDM is most common in German shepherd dogs (prevalence rate ** 2.01%) and also common in Pembroke Welsh Corgis (prevalence rate 0.58%), boxers (prevalence rate 0.59%), Chesapeake Bay retrievers (prevalence rate 0.83%), Rhodesian ridgebacks (prevalence rate 0.74%) and collie (prevalence rate 0.38%), and less common in several other breeds. While CDM is not common in the cavalier King Charles spaniel *** , it has been determined to be an inherited neurologic disorder caused by a mutation of the SOD1 (superoxide dismutase 1) emzyme. The SOD1 mutation appears to cause a mis-folding of proteins, resulting in an accumulation of toxic by-products in the axon (nerve fibers which transmit information to different neurons). These toxic by–products disrupt axoplasmic flow, eventually destroying myelin and ultimately replacing normal axons with astrogliosis (an abnormal increase in the number of astrocytes due to the destruction of nearby neurons).
Interestingly, it appears that not all cavaliers carrying two copies of the SOD1 mutation will develop the disease. So, there is much more to be learned about this disorder in the CKCS.
CDM initially attacks the nerve cells (neurons) in the spinal cord which control muscle movements in the hindquarters, causing at least partial loss of coordination and voluntary movement and sensory function (ataxia).
* CDM is also known as chronic degenerative radiculomyelopathy.
** Prevalence rates were calculated on the number of dogs presented to veterinary teaching hospitals in North America between January 1990 and December 1999.
*** However, in a February 2014 study of 73 CKCSs, 49.3% were found to have two of the genetic mutation (SOD1) associated with CDM, and another 37% were carriers of the mutation. See more about this study in the DNA testing section below.
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The disease itself does not produce pain, but the physical injuries it can cause to the dog certainly can be painful.
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Diagnosis of CDM can be very difficult because it calls for the elimination of other mimicking disorders. Among them is intervertebral disc disease, which is common in the cavalier King Charles spaniel, and arthritis because of the dog's usual advanced age. as well as degenerative lumbosacral stenosis, spinal cord neoplasia, spinal cysts, boney compressive lesions, caudal cervical spinal cord, orthopedic problems, and infections. Routine blood work, x-rays, and biochemistry typically will reveal no abnormalities. Cerebrospinal fluid (CSF) analysis is limited to exclude other neurological disorders.
Magnetic resonance imaging (MRI) and computerised tomography (CT) scans are performed only to rule out other diseases. Electro-physiological studies such as electromyography (EMG) and motor nerve conduction velocities (MNCV) do not detect abnormalities early in the disease, but EMG may show multifocal spontaneous activity in later stages.
The only way to confirm the diagnosis of CDM is by examination of the spinal cord after the dog dies.
In a February 2017 article, an American research team studied the fluid biomarker phosphorylated neurofilament heavy (pNF-H), a structural protein of myelinated axons, of 53 DM-affected dogs (no CKCSs) in various stages of DM. Their results suggest that pNF-H is a sensitive biomarker for diagnosis of DM, but that further study with a larger cohort is recommended.
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DNA Testing
Nevertheless, genotype analysis based on this mutation has been developed and is commercially available as a diagnostic test for CDM. The SOD1 genotyping test, in conjunction with clinical investigations, has significantly
improved the disease's prediction. The test will enable breeders to identify dogs that carry the genetic risk factor so that they can avoid matings that will produce puppies that are at increased risk of developing CDM as they age.
In a 2014 study, the mutation of the SOD1 gene has been identified in the cavalier King Charles spaniel. The exact frequency of this disease and approximate age of disease onset are unreported for the CKCS. However, in that study, 37% out of 73 cavaliers tested were carriers of the mutation, and 49.3% were at-risk or affected. In that study, however, there is no indication as to how the 73 cavaliers were selected. These extremely high percentages are vastly different from objective breed-wide statistical studies, such as the UK study from 1990 to 1999, which showed the highest percentage of affected German shepherd dogs at 2.01%.
The genetic test of the SOD1 gene in cavaliers should determine whether a dog is a genetic carrier of CDM. The disorder is believed to be inherited in an autosomal recessive manner in dogs, meaning that they must receive two copies of the mutated gene -- one from each parent -- to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same mutation, there is a risk of producing affected offspring. Theoretically, each puppy that is born to this pairing has a 25% chance of inheriting two copies of the SOD1 gene mutation and being at risk for the disease, and a 50% chance of inheriting one copy and being a carrier of the SOD1 gene mutation.
Test kits for CDM in cavaliers are available at:
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Nevertheless, it is possible to maintain the dog’s quality of life for a short time through nutrition and exercise. Well-balanced diets of fresh, unprocessed (no dry foods or kibble) food have been recommended. Regular exercise, such as walking and swimming, is recommended to maintain the dog’s ability to walk.
Physical therapy, including active and passive exercise, massage, hydrotherapy, and paw protection, is designed to maintain joint range of motion, may slow development of muscle atrophy, maintain neuromuscular function, and improve quality of life and may prolong the length of time that the dog remains mobile and increase survival time. See this July 2006 article.
Acupuncture and herbal therapies may help slow CDM's progression, improve the dog's quality of life, and relieve any gastro-intestinal symptoms. See this 2015 article for recommended alternative care treatments.
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Breeders' Responsibilities
Canine degenerative myelopathy is considered a heritable disease, and therefore affected cavaliers should not be bred. All cavalier breeding stock should be tested for CDM. See the DNA Testing section above for details.
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What You Can Do
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Research News
July 2017: Neurologist Dr. Coates of Univ. of Missouri needs DM-affected dogs for clinical trial. 
March 2017: Cummings School (Tufts) researchers need DM-affected dogs for an engineered adenovirus study. 
February 2017: USA researchers find promising CSF biomaker for early diagnosis of DM. In a February 2017 article, an American research team studied the fluid biomarker phosphorylated neurofilament heavy (pNF-H), a structural protein of myelinated axons, of 53 DM-affected dogs (no CKCSs) in various stages of DM. Their results suggest that pNF-H is a sensitive biomarker for diagnosis of DM, but that further study with a larger cohort is recommended.
February 2014: Mutant gene for canine degenerative myelopathy is identified in the CKCS and other breeds. In a February 2014 study, researchers have identified the mutation of the Sod1 gene believed to be associated with canine degenerative myelopathy, in the cavalier King Charles spaniel and 123 other purebred breeds. 73 cavaliers were included in the study, of which 49.3% were found to be have a pair of the mutation and were therefore deemed to be "at risk" for CDM, and another 37% of CKCSs were found to have one of the mutations and therefore deemed to be "carriers".
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Related Links
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Veterinary Resources
Degenerative myelopathy in the aging German Shepherd dog: clinical and pathologic findings. Averill D.R. Jr. J Am Vet Med Assoc. June 1973;62(12):1045-51.
Degenerative Myelopathy. Roger M. Clemmons. Small Anim. Pract. July 1992;22(4):965-971. Quote: Degenerative myelopathy (DM) is a neurodegenerative disease that is seen particularly in the German Shepherd. DM is a specific disorder characterized by widespread myelin and axon loss beginning in the thoracolumbar area of the spinal cord. The age of onset of DM is between 5 and 7 years. It may be confused with other disorders, including intervertebral disc protrusions, lumbosacral stenosis, and hip dysplasia, which also occur in older dogs. Most of the information about the pathophysiology and immunology of DM has come from studies of German Shepherds afflicted with the disease. . DM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA [aminocaproic acid] medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in OM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available.
Central nervous system pathology in 25 dogs with chronic degenerative radiculomyelopathy. R E. J. Johnston, J. A. Barrie, M. C. Mcculloch, T. J. Anderson, I. R. Griffiths. Vet.Rec. 2000;146:629-633. Quote: "The neuropathology of 20 German shepherd dogs and five German shepherd dog crosses with chronic degenerative radiculomyelopathy were analysed by conventional techniques, immunocytochemistry and electron microscopy. There were previously unrecognised changes in brain nuclei. In the spinal cord, both motor and sensory tracts were involved, principally in their more distal regions. Wallerian degeneration affected the corticorubrospinal pathways in the lateral columns and the ventral funiculi, predominantly in the caudal thoracic and lumbar segments, although more cranial involvement was also observed. The dorsal columns were affected in the caudal lumbar region and the cervical fasciculus gracilis. The regional distribution was variable between cases. Within the brain, abnormalities, including chromatolysis, gliosis and neuronal loss were observed in the red nucleus, lateral vestibular nucleus and, occasionally, in the dentate nucleus. The changes in brain nuclei were compared with those found in dogs at various times after a focal spinal injury. The neuronal changes in the brain may be related to the primary site of damage, and possible aetiological mechanisms are discussed."
Daily Controlled Physiotherapy Increases Survival Time in Dogs with Suspected Degenerative Myelopathy. I. Kathmann, S. Cizinauskas, M.G. Doherr, F. Steffen, A. Jaggy. J.Vet.Int.Med. July 2006;20(4):927-932. Quote: "The purposes of the study reported here were to evaluate the signalment and clinical presentation in 50 dogs with degenerative myelopathy, to evaluate whether mean survival time was significantly affected by various means of physiotherapy performed in 22 dogs, and to determine whether neurologic status, anatomic localization, or age at onset had an influence on survival time in dogs that received physiotherapy. We found a significant (P < .05) breed predisposition for the German Shepherd Dog, Kuvasz, Hovawart, and Bernese Mountain Dog. Mean age at diagnosis was 9.1 years, and both sexes were affected equally. The anatomic localization of the lesion was spinal cord segment T3-L3 in 56% (n = 28) and L3-S3 in 44% (n = 22) of the dogs. Animals that received intensive (n = 9) physiotherapy had longer (P < .05) survival time (mean 255 days), compared with that for animals with moderate (n = 6; mean 130 days) or no (n = 7; mean 55 days) physiotherapy. In addition, our results indicate that affected dogs which received physiotherapy remained ambulatory longer than did animals that did not receive physical treatment."
Efficient mapping of mendelian traits in dogs through genome-wide association. Elinor K Karlsson, Izabella Baranowska, Claire M Wade1, Nicolette H C Salmon Hillbertz, Michael C Zody, Nathan Anderson, Tara M Biagi, Nick Patterson, Gerli Rosengren Pielberg, Edward J Kulbokas III, Kenine E Comstock, Evan T Keller, Jill P Mesirov, Henrik von Euler, Olle Kämpe, Åke Hedhammar, Eric S Lander, Göran Andersson, Leif Andersson, Kerstin Lindblad-Toh. Nature Genetics. Sept. 2007;39:1321 - 1328. Quote: "With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with
27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only
20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of
100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health."
Evaluation of a proposed therapeutic protocol in 12 dogs with tentative degenerative myelopathy. Zoe S. Polizopoulou, Alexander F. Koutinas, Michael N. Patsikas, Nektarios Soubasis. Acta Vet. Hungarica. Sept. 2008;56(3):292-301. Quote: "The objective of this work was to evaluate the long-term efficacy of a proposed therapeutic protocol in 12 dogs with a tentative diagnosis of degenerative myelopathy, followed-up for a 6-month period. Twelve dogs fulfilling the antemortem inclusion criteria (breed, age, adequate vaccination, history of progressive posterior ataxia and/or paraparesis, no radiographic and myelographic abnormalities in the spinal cord and vertebral column) were allocated. All these dogs presented signs of thoracolumbar syndrome (T3-L3), scored as grade I (mild to moderate ataxia and paraparesis) in 10 and grade II (severe ataxia and ambulatory paraparesis) in 2 cases. Treatment included the use of ɛ-aminocaproic acid and N-acetylcysteine, supplemented with vitamins B, C and E. Prednisolone was given for the first two weeks and upon worsening of neurological signs. Daily exercise, performed as walking or swimming, was strongly recommended. Clinicopathological evaluation was normal in all 12 dogs, and survey radiographs and myelograms did not show spinal cord compression. Magnetic resonance imaging (MRI), performed only in 4 dogs, did not disclose compressive disorders or intramedullary lesions. Neurological signs were progressively worsening in all 12 animals, eventually resulting in severe paraparesis (grade III) or paraplegia (grade IV). The applied medications do not appear to be an attractive alternative to conservative management (physiotherapy) or euthanasia in canine degenerative myelopathy, irrespective of its chronicity."
Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Tomoyuki Awano, Gary S. Johnson, Claire M. Wade, Martin L. Katz, Gayle C. Johnson, Jeremy F. Taylor, Michele Perloski, Tara Biagi, Izabella Baranowska, Sam Long, Philip A. March, Natasha J. Olby, G. Diane Shelton, Shahnawaz Khan, Dennis P. O’Brien, Kerstin Lindblad-Toh, Joan R. Coates. PNAS. February 2009;106(8):2794-2799. Quote: "Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS."
Degenerative myelopathy – diagnosis and treatment (Proceedings). Joan R. Coates. dvm360.com August 2009. Quote: "Canine degenerative myelopathy (DM) is a spontaneously occurring, adult-onset, progressive spinal cord disease. Degenerative myelopathy was first described by Averill as a spinal cord disorder that predominates in German Shepherd dogs. If decreased pelvic limb reflexes are observed, nerve root involvement is presumed and the disease termed chronic degenerative radiculomyelopathy. Initially thought to be specific to the GSD, it also was designated German Shepherd Dog myelopathy. This disease is not uncommon in some pure bred dogs with an overall prevalence rate of 0.19%. Although the German Shepherd Dog is the most commonly affected breed, DM has been reported in other breeds and most recently in the Pembroke Welsh Corgi (PWC). Higher disease prevalence has been determined in a number of other purebred dogs, such as the Boxer, Rhodesian Ridgeback, and Chesapeake Bay Retriever."
Prediction and Diagnosis of Canine Degenerative Myelopathy. Inventors: Joan R. Coates, Kerstin Lindblah-Toh, Claire Wade, Gary S. Johnson. US Patent Nr. 12/365,578. Sept. 2009. Quote: "The present invention provides for methods of identifying a dog carrying a major genetic risk factor in the SOD1 gene for degenerative myelopathy, a potential model for human amyeotrophic lateral sclerosis. Also provided a methods of early diagnosis, treatment and breeding based on the presence or absence of the marker."
Canine Degenerative Myelopathy. Joan R. Coates. Vet. Clinics of No. America. 2010. Quote: "Canine degenerative myelopathy (DM) was first described in 1973 by Averill as an insidious, progressive, general proprioceptive (GP) ataxia and upper motor neuron (UMN) spastic paresis of the pelvic limbs beginning in late adulthood, ultimately leading to paraplegia and necessitating euthanasia. Until recently, presence of primary axonal degeneration and nerve fiber loss that was restricted to spinal cord white matter and most severe in the mid to caudal thoracic region was compatible with a diagnosis of DM. The disease was termed “degenerative myelopathy” because of its histopathologic nature as a nonspecific degeneration of spinal cord tissue of undetermined cause. In 1975, Griffiths and Duncan published a series of cases with similar clinical signs and histologic changes in the white matter. They also reported hyporeflexia and nerve root involvement, and they termed the condition chronic degenerative radiculomyelopathy. Though most of the dogs in these initial reports were German Shepherd Dogs (GSD), other breeds were represented. Nonetheless, for many years, DM was considered an UMN and GP disease in the GSD. More recently DM has been recognized as a common problem in a number of breeds with an overall prevalence of 0.19%. Additionally, the clinical spectrum of DM has been broadened to involve both the UMN and lower motor neuron (LMN) systems. A recent advance in the molecular genetics of DM indicates that this canine disease may share pathogenic mechanisms with some forms of human amyotrophic lateral sclerosis (ALS – Lou Gehrig’s disease)."
Development of a motor unit number estimation technique in normal dogs: a potential biomarker for canine degenerative myelopathy. Laura Vasquez. Univ. of Missouri. May 2011. Quote: "Motor unit number estimation (MUNE) is an electrophysiologic technique for quantifying the lower motor neuron (LMN) system. MUNE has proven useful in evaluating and monitoring neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Recently a missense mutation in the canine superoxide dismutase 1 (SOD1) gene has been shown to be a risk factor for canine degenerative myelopathy (DM) suggesting homology to familial SOD1 ALS. To date, the LMN component of DM has not been well characterized or quantified. The modified incremental stimulation MUNE technique was applied to the sciatic-deep peroneal nerve branch with bilateral recordings at the extensor digitorum brevis muscle of 17 clinically normal dogs. Mean (± SD) value for the entire MUNE pool was 51 ± 21 with a range from 8 to 154. No statistically significant difference was noted between pelvic limbs (P=0.14) or between different age groups (< 7years old or >= 7 years old) (P=0.17). Test-retest reliability was assessed for trials performed under different anesthetic episodes (intermittent) versus trials performed under the same anesthetic episode (consecutive). The intraclass correlation coefficients for consecutive and intermittent MUNE evaluations were 0.73 and 0.65, respectively. These results provide preliminary reference ranges for normal dogs and document the potential utility of EDB modified incremental stimulation MUNE for longitudinal monitoring of lower motor neuron loss in DM affected dogs."
The establishment of potential cerebrospinal fluid biomarkers for canine degenerative myelopathy. Shafie, Intan Nur Fatiha. Glasgow Theses Service. May 2013. Quote: "Canine degenerative myelopathy(DM) is a late onset neurodegenerative disease that primarily affects German Shepherd dog (GSD), though a number of other specific breeds are also affected. Other small breeds that have been reported with DM include Cavalier King Charles Spaniels. The underlying cause of the disorder remains elusive, though recent advances have implicated a mutation of superoxide dismutase 1(Sod1) in the aetiology, also implying DM is a potential orthologue of human amyotrophic lateral sclerosis. The identification of the Sod1 mutation raises the index of suspicion for an individual animal, however it is not specifically diagnostic as a proportion of dogs homozygous for the Sod1 mutation do not develop DM. Therefore, there is a clinical need for the development of specific biomarker(s) for DM to support genetic test. The aim of this study was to establish potential biomarkers for DM by exploring canine cerebrospinal fluid (CSF). A dual strategy was adopted;1) Evaluation of potential ALS biomarkers in DM CSF, 2) Identification of novel biomarker(s) in DM CSF. The cases selected in this project had a presumptive diagnosis of DM and were homozygous for Sod1 mutation [including one cavalier King Charles spaniel]. Preliminary characterisation by Western blot and mass spectrometry identified four protein candidates in DM CSF, comprised of cystatin C, transthyretin (dimeric and monomeric TTR), haptoglobin and clusterin. Since the validity of these putative biomarkers may be influenced by pre-analytical variables that may arise from the clinical environment, we therefore assessed the impact of three potential sample handling practices on these four proteins. The results from these experiments demonstrate that dimeric TTR and clusterin were affected by sample handling conditions. Therefore, an appropriate protocol for CSF sample handling was established. Western blot analyses indicated that clusterin is the most viable biomarker candidate for DM. Clusterin was significantly elevated in DM CSF when compared to a range of neurological conditions. The second potential candidate for DM biomarker is TTR, which is potentially reduced, an observation similar to those found in ALS CSF. The relationship of these proteins in the pathogenic mechanisms that underpin DM is unclear. However, based on observations on ALS, it is reasonable to speculate that their alterations are associated with a toxic gain of function of the mutant SOD1 protein. The successful characterisation of clusterin and TTR in DM CSF may therefore represent components of a panel of emerging biomarkers that may combine to distinguish DM in the clinic and provide further insights into the disease mechanisms."
Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. R. Zeng, J.R. Coates, G.C. Johnson, L. Hansen, T. Awano, A. Kolicheski, E. Ivansson, M. Perloski, K. Lindblad-Toh, D.P. O’Brien, J. Guo, M.L. Katz, G.S. Johnson. J Vet Intern Med. February 2014;28:515–521. Quote: "Background: Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported. Objective: To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds. Animals: DNA from 33,747 dogs [including 73 cavalier King Charles spaniels] was genotyped at SOD1:c.118, SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined. Methods: Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias. Results: The SOD1:c.118A allele was found in cross-bred dogs and in 124 different canine breeds [including the CKCS] whereas the SOD1: c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1: c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes. [Of the 73 CKCSs, 10 (13.7%) were normal with no mutant allele; 27 (37%) were carriers of one of the mutant allele with a 50% chance of passing it on; and 36 (49.3%) had two of the mutant alleles and were at risk of developing signs of CDM and would pass the mutant allele on to its offspring.] Conclusions and Clinical Importance: We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy."
A retrospective study of the prevalence of the canine degenerative myelopathy associated superoxide dismutase 1 mutation (SOD1:c.118G > A) in a referral population of German Shepherd dogs from the UK. Angela L Holder, James A Price, Jamie P Adams, Holger A Volk and Brian Catchpole. Canine Genetics & Epidemiology. Sept. 2014. Quote: "Background: Canine degenerative myelopathy (CDM) is an adult onset, progressive neurodegenerative disease of the spinal cord. The disease was originally described in the German Shepherd dog (GSD), but it is now known to occur in many other dog breeds. A previous study has identified a mutation in the superoxide dismutase 1 gene (SOD1:c.118G > A) that is associated with susceptibility to CDM. In the present study, restriction fragment length polymorphism (RFLP) analysis was used to genotype GSD for SOD1:c.118G > A in order to estimate the prevalence of the mutation in a referral population of GSD in the UK. Results: This study demonstrated that the RFLP assay, based on use of PCR and subsequent digestion with the Eco571 enzyme, provided a simple genotyping test for the SOD1:c.118G > A mutation. In a young GSD population (i.e. dogs less than 6 years of age, before clinical signs of the disease usually become apparent), 8 of 50 dogs were found to be homozygous and a further 19 were heterozygous for the mutation. In dogs over 8 years of age, 21 of 50 dogs admitted to a tertiary referral hospital with pelvic limb ataxia as a major clinical sign were homozygous for the mutation, compared to none of 50 dogs of similar age, but where no neurological disease was reported on referral. Conclusions: This data suggests that genotyping for the SOD1:c.118G > A mutation is clinically applicable and that the mutation has a high degree of penetrance. Genotyping might also be useful for screening the GSD population to avoid mating of two carriers, but since the allele frequency is relatively high in the UK population of GSD, care should be taken to avoid reduction in genetic diversity within the breed."
Integrative Management of Degenerative Myelopathy. Angela Casey, Thomas Pfafman, Alexandra Mittner. Integrative Vet. Care J. 2015. Quote: A multifaceted treatment protocol is required for this multifaceted disease model. The greatest benefit is seen with early intervention. Case reports suggest that the progress of DM can be consistently slowed, halted or even temporarily reversed.
Variants within the SP110 nuclear body protein modify risk of canine degenerative myelopathy. Emma L. Ivansson, Kate Megquier, Sergey V. Kozyrev, Eva Murén, Izabella Baranowska Körberg, Ross Swofford, Michele Koltookian, Noriko Tonomura, Rong Zeng, Ana L. Kolicheski, Liz Hansen, Martin L. Katz, Gayle C. Johnson, Gary S. Johnson, Joan R. Coates, Kerstin Lindblad-Toh. PNAS. May 2016;113(22):E3091-3100. Quote: Canine degenerative myelopathy (DM) is a naturally occurring neurodegenerative disease with similarities to some forms of amyotrophic lateral sclerosis (ALS). . We previously showed that DM is a promising model for ALS, because genome-wide association identified a mutation in superoxide dismutase 1 gene (SOD1), a known ALS gene. This mutation found in many dog breeds increases the risk of DM, and the pathological findings and clinical progression of the two diseases are similar. In this study, we identify a modifier gene, SP110 nuclear body protein (SP110), which strongly affects overall disease risk and age of onset in Pembroke Welsh Corgis at risk for DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients. . Most dogs that develop DM are homozygous for a common superoxide dismutase 1 gene (SOD1) mutation. However, not all dogs homozygous for this mutation develop disease. We performed a genome-wide association analysis in the Pembroke Welsh Corgi (PWC) breed comparing DM-affected and -unaffected dogs homozygous for the SOD1 mutation. The analysis revealed a modifier locus on canine chromosome 25. A haplotype within the SP110 nuclear body protein (SP110) was present in 40% of affected compared with 4% of unaffected dogs (P = 1.5 × 10−5), and was associated with increased probability of developing DM (P = 4.8 × 10−6) and earlier onset of disease (P = 1.7 × 10−5). SP110 is a nuclear body protein involved in the regulation of gene transcription. Our findings suggest that variations in SP110-mediated gene transcription may underlie, at least in part, the variability in risk for developing DM among PWCs that are homozygous for the disease-related SOD1 mutation. Further studies are warranted to clarify the effect of this modifier across dog breeds. . The aim of the present study was to identify genetic modifiers of disease risk in dogs that are predisposed to DM by being homozygous for the SOD1 risk allele. We report that variants within SP110 modify the genetic risk and age of onset of DM in PWC dogs homozygous for mutant SOD1, and that those variants contribute to changes in the SP110 gene regulation and isoform ratio expressed in blood cells.
Dm hund
Foreningens medlemmer består af polititjenestemænd med politiets patruljehunde (sektion I) og civile og polititjenestemænd med civile hunde(sektion II). Desuden har foreningen en række passive medlemmer.
- at skabe interesse for opdræt og dressur af politihunde og deres praktiske anvendelse inden for politiets arbejde og blandt civile medlemmer.
The OptiGen prcd-PRA Test Code 105
The OptiGen prcd-PRA test is a DNA-based test that helps you avoid one form of Progressive Retinal Atrophy (PRA). PRA refers to a group of diseases that cause the retina of the eye to degenerate slowly over time. The result is declining vision and eventual blindness. “prcd” stands for “progressive rod-cone degeneration” which is the type of PRA known in several breeds. AFTER reading the information on this page, you can link to information specifically about the breed in which you are interested.
Genetic Registries – genetic registries have been established for several breeds. For these breeds results are shared with OFA, CERF or with a breed designated registry. We have noted below with an asterisk which breeds are included. This policy applies only to those registries that are in effect at the time the test is requested.
- Cocker Spaniel (American)
- American Eskimo Dog
- Australian Cattle Dog
- Australian Cobberdog
- Australian Shepherd
- Australian Shepherd, Miniature & Toy
- Australian Stumpy Tail Cattle Dog
- Barbet
- Bolognese
- Lab/Golden Cross
- Labradoodle
- Labradoodle, Australian
- Labradoodle/Goldendoodle Cross
The genetic disorder, prcd-PRA , causes cells in the retina at the back of the eye to degenerate and die, even though the cells seem to develop normally early in life. The “rod” cells operate in low light levels and are the first to lose normal function. Night blindness results. Then the “cone” cells gradually lose their normal function in full light situations. Most affected dogs will eventually be blind. Typically, the clinical disease is recognized first in early adolescence or early adulthood. Since age at onset of disease varies among breeds, you should read specific information for your dog. Diagnosis of retinal disease can be difficult. Conditions that seem to be prcd-PRA might instead be another disease and might not be inherited. OptiGen’s genetic test assists in making the diagnosis. It’s important to remember that not all retinal disease is PRA and not all PRA is the prcd form of PRA. Annual eye exams by a veterinary ophthalmologist will build a history of eye health that will help to diagnose disease.
Unfortunately, at this time there is no treatment or cure for PRA. If your dog is affected, you may find it helpful to read about other owners’ experiences living with blind dogs. (suggested links: www.eyevet.org and www.blinddogs.com )
Inheritance
Prcd-PRA is inherited as a recessive trait. This means a disease gene must be inherited from each parent in order to cause disease in an offspring. Parents were either “carrier” or affected. A carrier has one disease gene and one normal gene, and is termed “heterozygous” for the disease. A normal dog has no disease gene and is termed “homozygous normal” – both copies of the gene are the same. And a dog with two disease genes is termed “homozygous affected” – both copies of the gene are abnormal.
It’s been proven that all breeds being tested for prcd-PRA have the same disease caused by the same mutated gene. This is so, even though the disease might develop at different ages or with differing severity from one breed to another.
Although prcd-PRA is inherited, it can be avoided in future generations by testing dogs before breeding. Identification of dogs that do not carry disease genes is the key. These "clear" dogs can be bred to any mate - even to a prcd-affected dog which may be a desirable breeding prospect for other reasons. The chance of producing affected pups from such breedings depends on the certainty of test results. Again, you’ll find the specific information on certainty of test results for your dog by linking to breed specific information.
The Genetic Test
The OptiGen prcd test is done on a small sample of blood from the dog. The test analyzes the specific DNA mutation causing prcd-PRA. The OptiGen test detects the mutant, abnormal gene copy and the normal gene copy. The result of the test is a genotype and allows separation of dogs into three groups: Normal/Clear (homozygous normal), Carrier (heterozygous) and Affected (homozygous mutant).
low risk of producing affecteds
Clear to remove risk of producing
Clear to remove risk of producing
Breeding Strategies
Benefits & Limits to All Genetic Testing
How you can participate
The prcd-PRA test is done on a small sample of blood obtained by your veterinarian. This allows the lowest risk of contamination of the sample and added assurance of a match of the sample with the identified dog. Please read Instructions and Information to learn about ordering a test, shipping a sample and prices.
Affected dogs are tested at no charge . Please review the conditions for this before submitting a sample from an affected dog.
Registries: Breed clubs may sponsor genetic disease registries and OptiGen may provide some test information directly to the registry in accordance with the club’s official policies. Please go to your club to learn more about this.
The research leading to this discovery was undertaken by scientists at the James A. Baker Institute of Animal Health at Cornell University's College of Veterinary Medicine in Ithaca, New York. Initial data are published in volume 95 of the March, 1998 issue of the Proc. National Academy of Sciences. Publication of the prcd mutation is being prepared. The patented technology underlying this test is under exclusive license to OptiGen from Cornell Research Foundation, Inc.
Program
kl. 18.00 Indmarch, DM åbnes,
kl. 18.30 Lodtrækning
kl. 8.00 Konkurrencen starter
kl. ca.19.00 Første konkurrencedag slut
kl. 8.00 Konkurrence starter
kl.16.00 Konkurrencen slutter
kl.16.30 Afslutning med hund
kl. 18.00 Afslutning og spisning.
Kåring af bedste gr. A, B og C
Tidspunkterne er foreløbige og vil blive tilpasset, når deltager- antallet er kendt.
Information om deltagergebyr:
Tilmeldingsgebyr 500 kr.
Tilmeldingen er bindende og først godkendt, når betalingen er registreret.
Tilmeldingsgebyret overføres til konto: 3420 - 4357807565.
Sponsorer og tilmeldte
Vi tilbyder en standplads inkl. annonce i kataloget, på hjemmesiden.
Sponsorater og støtte af enhver art til pokaler og præmier modtages med stor tak og kan indsættes på kto.: 3420 - 4357807565
Hundetræning for alle hunde og deres ejere.
Danmarks civile Hundeførerforening er en forening til alle der holder af hunde, og som gerne vil træne med deres hund. Måske skal den bare lære almindelig lydighed – eller du har måske ambitioner om at stille op til konkurrencer i Agility, IPO, Lydighed, Nordisk, Rally Lydighed eller Sporhundeprøve. Lige meget hvilken hund du har, og hvor store ambitioner du har på dens vegne, er der plads til dig i Danmarks civile Hundeførerforening.
Hvis du gerne vil gå til træning med din hund? Så skal du henvende dig i en af DcH’s lokalforeninger, det er her det egentlige hundearbejde foregår. Her går hunden til træning med sin ejer ca. 1 gang om ugen. For de mere konkurrence interesserede afholdes der lokale prøver og konkurrencer. Lokalforeningen arrangerer også foredrag, fester, gåture m.m. Hunden vil lærer den mest elementære lydighed på begynderholdene , såsom at komme, når du kalder og gå pænt i snor. Desuden vil der være forskellige andre øvelser, som vil styrke samarbejdet mellem hund og fører. Hunde der træner i DcH har den fordel, at de lærer at begå sig socialt blandt mange forskellige racer og blandinger.
Du vil under træningen kunne få hjælp til at løse mange problemer, som du kan have med hunden i hverdagen. DcH har et frivilligt korps af Hundeadfærdskonsulenter som står til rådighed for alle hundeejere, og de vil gerne hjælpe med alle problemer, store som små. Udover almindelig lydighedstræning tilbyder lokalforeninger også træning i DcH’s konkurrenceprogram og mange steder tilbydes der træning i Agility og Rally. Enkelte foreninger har endvidere træning i IPO og sporhundeprøver (SPH) og i det nordiske program.
DcH råder også over en frivillig Eftersøgningstjenneste. Eftersøgningshundene er special uddannet til at finde tabte ting, så som punge, nøgler, briller, høreapparater m.m. Se mere her.
Har du lyst til at komme til træning med din hund, kan du finde kontaktoplysninger på den nærmeste DcH lokalforening her. Og ellers kan du henvende dig til DcH’s sekretariat på telefon 2115 6610
Degenerative Myelopathie (DM) Exon 2
Degenerative Myelopathie (DM) Exon 2
Erkrankung
Die canine degenerative Myelopathie (DM) ist eine schwere neurodegenerative Erkrankung mit spätem Beginn ungefähr ab dem 8. Lebensjahr. Die Erkrankung ist durch eine Degeneration der Axone und des Myelins im Brust- und Lendenteil des Rückenmarks gekennzeichnet, was eine progressive Ataxie und Parese verursacht. Man beobachtet die ersten klinischen Anzeichen in der Hinterhand als Zeichen einer Störung des oberen Motoneurons. Es entwickelt sich eine unkoordinierte Bewegung der Hinterhand, eine gestörte Eigenwahrnehmung und gestörte Reflexe. Wenn die Erkrankung weiter fortschreitet, weitet sie sich auf die vorderen Gliedmaßen aus und manifestiert sich als schlaffe Parese und Paralyse. Die Degenerative Myelopathie wurde zuerst als eine Rückmarkserkrankung insbesondere beim Deutschen Schäferhund beschrieben. Neben dem Deutschen Schäferhund sind aber viele weitere Rassen von der degenerativen Myelopathie betroffen.
Als Risikofaktor für die Entwicklung einer DM wurde eine Mutation im Exon 2 des SOD1-Gens bei vielen Rassen nachgewiesen. Bei Berner Sennenhunden gibt es zusätzlich eine Mutation im Exon 1 dieses Gens, die ebenfalls mit der DM in Zusammenhang steht. Für den Berner Sennenhund können beide Mutationen untersucht werden. Die Anforderung kann zusammen oder einzeln erfolgen.
Erbgang
autosomal-rezessiv mit altersabhängiger unvollständiger Penetranz;
Nachgewiesen wird ein Risikofaktor, der mit der DM assoziiert ist.
3-5 Werktage nach Erhalt der Probe
* Tous les prix indiqués comprennent la TVA au taux légal en vigueur. Pour la livraison à l'intérieur de l'Allemagne, nous prenons en charge les frais d'expédition.
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