Degenerative Myelopathy
Sod1b in Bernese Mountain Dogs

Degenerative myelopathy (DM) is a progressive neurological disorder that affects the spinal cord in dogs, particularly Bernese Mountain Dogs. DM is caused by a mutation in the SOD1B gene, which codes for an enzyme called superoxide dismutase 1. This enzyme plays a vital role in protecting cells from oxidative stress, which is the damage caused by excess free radicals in the body.

The SOD1B mutation leads to a deficiency of this enzyme, which leads to the accumulation of free radicals and the development of DM. Symptoms of DM typically begin to appear in affected dogs when they are around 7 to 14 years old and may include weakness in the hind legs, difficulty standing or walking, and loss of coordination. The disease progresses over time, and affected dogs may eventually lose the use of their hind legs and become paralyzed.

There is no cure for DM, and treatment is primarily supportive, including physical therapy and the use of assistive devices such as wheelchairs. It is important for owners of Bernese Mountain Dogs to be aware of the risk of DM and to discuss this with their veterinarian. There are genetic tests available that can determine whether a dog is at risk for developing DM, and breeding programs can use this information to reduce the frequency of the disease in the breed.

This test is offered by these labs: GenSol, Neogen / Paw Print Genetics, Paw Print Genetics, University of Missouri

DM is a genetic disease inherited in an autosomal recessive manner meaning that the dog must receive the mutated gene from both parents to develop the disease. The first signs of degenerative myelopathy generally develop at around eight years of age, although the onset maybe later in life in some dogs. Weakness and loss of coordination in one or both of the hind limbs (back legs) is often the initial sign, followed by dragging and scuffing of the digits (toes).

What are the common signs of degenerative myelopathy?

The first signs of degenerative myelopathy generally develop at around eight years of age, although the onset maybe later in life in some dogs. Weakness and loss of coordination in one or both of the hind limbs (back legs) is often the initial sign, followed by dragging and scuffing of the digits (toes). Affected dogs have a drunken appearance and will often stumble and fall when turning, especially on slippery surfaces. As the condition gradually progresses over many months, hind limb weakness and loss of coordination increase. In some severe cases, the forelimbs (front legs) also become affected and affected dogs can become unable to walk and may develop incontinence. Degenerative myelopathy is not a painful condition and, as a result, affected dogs are generally well and keen to exercise, despite their disability.

Degenerative myelopathy SOD1B (Bernese mountain dog type) is caused by a Mutation of the SOD1 gene currently only identified in the Bernese mountain dog. Bernese mountain dogs are known to develop a more slowly progressive form of degenerative myelopathy (DM) associated with this mutation. 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 having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the SOD1 gene mutation.

The average age of onset for dogs with DM is approximately nine years of age. The disease affects the White Matter tissue of the spinal cord and is considered the canine equivalent to amyotrophic lateral sclerosis (Lou Gehrig’s disease) found in humans. Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog but will progress until the dog is no longer able to walk. The gait of dogs affected with DM can be difficult to distinguish from those with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of DM, dogs may lose fecal and urinary continence and the forelimbs may be affected. Affected dogs may fully lose the ability to walk within 2 years after the onset of symptoms. Medium to large breed dogs that are affected with DM, such as the Bernese mountain dog, can be difficult to manage and owners often elect euthanasia when their dog can no longer support weight in the hind limbs.

The Genetics of DM

Two direct DNA tests, one for the A mutation and one for the B mutation, are available that apply to the Bernese Mountain Dog. Many laboratories can perform these two tests, which use DNA from a cheek swab. When the test for SOD1-A is done, a clear result only means that the two genes are clear of that specific SOD1-A mutation; the test for the SOD1-B mutation is necessary to complete the genetic picture. In Bernese it has been determined that the SOD1 gene will have either the A or B mutation, not both. If a Berner is at risk for SOD1-A (both copies of the SOD1 gene have the A mutation), then the DNA test for the SOD1-B mutation does not need to be done, and vice versa. If a Berner is clear or a carrier for one of the mutations, then the test for the other mutation must also be done in order to learn the actual status for both copies of the SOD1 gene.

Inheritance DM is inherited as an autosomal recessive trait with incomplete penetrance. Recessive means that both copies of the gene present in an individual dog have to contain a mutation. In other words, both the mother and father of the dog pass on this mutation to the offspring. The SOD1 gene is not located on the X or Y sex chromosomes, it’s on an autosomal (not sex-linked) chromosome. If a dog gets two mutated SOD1 genes (one from each parent), then that dog is said to be at risk for DM. Because not all of the at-risk dogs will become affected, the trait has incomplete penetrance.

Over half of the dogs that have been tested carry at least one copy of a mutated SOD1 gene. The allele frequency is the calculation of mutated genes as a percentage of all copies of the gene. So as many as 37% of all the available genes in the breed are mutated copies.

References:

• 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 Feb 24; 106(8):2794-9. [PubMed: 19188595]

• Coates JR, Wininger FA. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. 2010 Sep; 40(5):929-50. [PubMed: 20732599]

• Pfahler S, Bachmann N, Fechler C, Lempp C, Baumgärtner W, Distl O. Degenerative myelopathy in a SOD1 compound heterozygous Bernese mountain dog. Anim Genet. 2014 Apr;45(2):309-10. [PubMed: 24450472]