Cerebellar degeneration-myositis complex in Dutch Shepherds

CDMC combines symptoms of cerebellar degeneration and inflammatory myopathy. Affected dogs develop muscle tremors, stiffness of the pelvic limbs, muscle weakness progressing to inability to walk and severe muscle atrophy. Cerebellar ataxia (stumbling or lack of coordination) and hypermetria (abnormal walking with front legs extending higher than normal) were also observed. Muscle weakness and generalized muscle atrophy began to manifest at 3 to 9 months of age.

In the Dutch Shepherd Dog, this disease is caused by the missense mutation c.1046T>C in the SLC25A12 gene, which encodes an electrogenic aspartate-glutamate carrier in the mitochondria. Severe impairment of its transport activity due to the mutation leads to oxidative stress and the development of a pro-inflammatory environment in muscle.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Shelton, G.D., Minor, K.M., Li, K., Naviaux, J.C., Monk, J., Wang, L., Guzik, E., Guo, L.T., Porcelli, V., Gorgoglione, R., Lasorsa, F.M., Leegwater, P.J., Persico, A.M., Mickelson, J.R., Palmieri, L., Naviaux, R.K. : A mutation in the mitochondrial aspartate/glutamate carrier leads to a more oxidizing intramitochondrial environment and an inflammatory myopathy in Dutch shepherd dogs. J Neuromuscul Dis 6:485-501, 2019. Pubmed reference: 31594244