{"id":13575,"date":"2019-01-18T13:49:38","date_gmt":"2019-01-18T13:49:38","guid":{"rendered":"http:\/\/labgenvet.ca\/profil-maladie-canine-myelopathie-degenerative\/"},"modified":"2023-07-11T19:05:14","modified_gmt":"2023-07-11T19:05:14","slug":"canine-disease-profile-degenerative-myelopathy-dm","status":"publish","type":"post","link":"https:\/\/labgenvet.ca\/en\/canine-disease-profile-degenerative-myelopathy-dm\/","title":{"rendered":"Canine Disease Profile – Degenerative Myelopathy (DM)"},"content":{"rendered":"

Canine Disease Profile – Degenerative Myelopathy (DM)<\/h1>\n

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German Shepherd<\/span><\/div><\/div>\n

Written by Dr. David W. Silversides, DVM<\/p>\n

Degenerative Myelopathy (DM)<\/a> is a neuro-muscular degenerative disease caused by a specific gene mutation that has been identified in many dog breeds. \u00a0Additional genetic factors as well as environmental factors can also contribute to the time of onset and progression of the disease. \u00a0DM is a disease that affects the white matter of the spinal cord and is equivalent to Amyotrophic Lateral Sclerosis (ALS; also known as Lou Gehrig\u2019s disease) in humans.[\/vc_column_text][\/vc_column][\/vc_row][vc_row el_class=”bloc_info”][vc_column][vc_column_text]<\/p>\n

Clinical symptoms of degenerative myelopathy<\/h4>\n

Affected dogs usually start showing symptoms of progressive muscular atrophy by 7 to 9 years of age, with initial loss of coordination of the hind limbs. These dogs can lose mobility six months to two years after the onset of clinical signs, with large dogs showing a more rapid progression of symptoms than small dogs.<\/p>\n

Pain is not associated with the disease, and symptoms can progress to the point that the animal is incontinent and eventually paraplegic. \u00a0 There is no treatment and often the affected animal is euthanized for humanitarian reasons before these final stages.[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text]<\/p>\n

The genetics of Degenerative Myelopathy<\/h4>\n
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Bernese Mountain Dog<\/span><\/div><\/div>\n

DM in dogs is an example of a genetic disease that follows (more or less) simple or mendelian genetics.\u00a0 The DNA mutation that has been linked to DM is a simple substitution of one letter for another, found in the SOD1<\/em> gene. \u00a0This mutation has been identified in over 180 dog breeds, so I will not list them all.<\/p>\n

DM is considered an autosomal recessive disease with variable penetrance.\u00a0 Dogs from several breeds are particularly at risk of developing DM when the double mutation (M\/M) is present in an animal.\u00a0 These breeds include (among others) the German Shepherd, the Bernese Mountain Dog and the Boxer.<\/p>\n

Modifying genes for Degerative Myelopathy<\/h4>\n
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Corgi<\/span><\/div><\/div>\n

For some dog breeds, dogs can be M\/M for the mutation in the SOD1<\/em> gene, but whether or not they develop DM now depends on additional genetic factors known as modifying genes<\/strong>.<\/p>\n

A case in point is the Pembrooke Welsh Corgi.\u00a0 Corgis that are M\/M for the mutation of the SOD1<\/em> gene can show clinical signs of DM by the age of 7 to 9 years, or can be free of signs at 15 years of age.\u00a0\u00a0 The increased susceptibility seems to be due to the presence of a mutation within a modifying gene, and this modifying gene for Corgis has been identified.\u00a0 Unfortunately, modifying genes for other breeds, even if they are suspected, are not as yet identified.<\/p>\n

The Bernese Mountain Dog is another breed worth mentioning.\u00a0 In this breed, a second mutation within the SOD1<\/em> gene was identified that can cause increased risk of having DM.\u00a0 This second mutation is not seen in other breeds.\u00a0 So simple genetics isn\u2019t always so simple.\u00a0 The known genetics of DM in the dog pales in comparison to the known genetics of ALS in humans, where there are over 150 mutations documented within the human SOD1<\/em> gene, and at least 5 different modifying genes for ALS that have been identified.<\/p>\n

A recessive disease occurring later in life<\/h4>\n

There are several practical aspects concerning DM in dogs that are worth mentioning.\u00a0 It is a recessive disease that occurs later on in life, after the reproductive years of the animal.\u00a0 Of course, the M\/M double mutant animals showing symptoms are a problem.\u00a0 But an additional problem, particularly with respect to controlling the disease within a breed, are the unidentified carrier (M\/N) animals.<\/p>\n

If M\/N animals are unknowingly used for reproduction, there is a good chance that the mutation will be passed on to the next generation.\u00a0 More problematic, if two M\/N animals are bred together, there is a 1 in four chance of producing M\/M double mutant puppies at risk of developing DM later in their lives.\u00a0 These M\/M puppies exist because I have seen their DNA; I know that at the age of 7 to 9 years, they will be taken into a veterinary clinic because they are starting to get wobbly in the back end.\u00a0 And the disease cycle continues.<\/p>\n

Identifying carrier animals<\/h4>\n
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Boxer<\/span><\/div><\/div>\n

Although unidentified carrier animals are a problem, as soon as carrier animals are identified (usually by a DNA test), M\/N animals are much less problematic.\u00a0 Carrier animals are not at risk of developing DM, and if bred to N\/N clear animals there is no risk of producing M\/M double mutant puppies.\u00a0 As I like to tell breeders, identifying a carrier (M\/N) animal is good news, but of course the breeders would have preferred to have identified a clear (N\/N) animal.<\/p>\n

Be that as it may, due to the numbers of breeds of dog that have the SOD1<\/em> mutation, the frequencies of the mutation seen within breeds, the late age for disease onset, the rather complicated \u201csimple\u201d genetics of the disease as well as the decentralized nature of dog breeding, it will take many years before DM and its mutation are eliminated from our dog breeds.<\/p>\n

DNA sequencing profiles and frequencies<\/h4>\n

DNA sequencing profiles and frequencies of animals that are N\/N (clear), M\/N (carrier) and M\/M (double mutant) for the DM mutation, based on over 600 dogs tested at Labgenvet, are as follows:<\/p>\n

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For additional genetic information and references regarding Degenerative Myelopathy in dogs, please refer to the following link: https:\/\/labgenvet.ca\/en\/disease\/degenerative-myelopathy-dm-sod1\/.<\/a><\/p>\n

A comprehensive list of simple genetic diseases in dogs can be found at: https:\/\/labgenvet.ca\/en\/dog-genetic-disease-search\/<\/a>.<\/p>\n

[\/vc_column_text][\/vc_column][\/vc_row][vc_row el_class=”references”][vc_column][vc_column_text]References:<\/strong><\/p>\n

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  1. OMIA link [000263-9615<\/a>]<\/li>\n
  2. Awano T, Johnson GS, Wade CM, Katz ML et al. (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. PNAS 106(8), 2794-2799. [pubmed\/19188595<\/a>]<\/li>\n
  3. Zeng R, Coates JR, Johnson GC et al. (2014) Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. J Vet Intern Med 28(2):515-521. [pubmed\/24524809<\/a>]<\/li>\n
  4. Coates JR, Wininger FA. (2010) Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. 40(5):929-50. [pubmed\/20732599<\/a>]<\/li>\n
  5. Crisp MJ, Beckett J, Coates JR, Miller TM. (2013) Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis model. Exp Neurol. 248:1-9. [pubmed\/23707216<\/a>]<\/li>\n
  6. Holder AL, Price JA, Adams JP, Volk HA, Catchpole B. (2014) A retrospective study of the prevalence of the canine degenerative myelopathy associated superoxide dismutase 1 mutation (SOD1:c.118G\u2009>\u2009A) in a referral population of German Shepherd dogs from the UK. Canine Genet Epidemiol. 1:10. [pubmed\/26401327<\/a>]<\/li>\n
  7. Turba ME, Loechel R, Rombola E et al. (2017) Evidence of a genomic insertion in intron 2 of SOD1 causing allelic drop-out during routine diagnostic testing for canine degenerative myelopathy. Animal Genetics 48(3):365-368. [pubmed\/27917507<\/a>]<\/li>\n<\/ol>\n

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