Duchenne muscular dystrophy in Border Collies

Duchenne muscular dystrophy (DMD) is a disease characterized by progressive muscle weakness that is ultimately fatal. Clinical signs begin to appear in puppies between 8 and 10 weeks of age and include a stiff gait or shortened stride, inability to fully open the jaw, difficulty swallowing, excessive salivation and marked wasting of the muscles of the body and limbs.

Duchenne muscular dystrophy is caused by a mutation in the DMD gene encoding dystrophin. Dystrophin is a cytoskeletal protein found mainly in smooth, cardiac, and skeletal muscles and in neurons in specific areas of the central nervous system. It mediates communication between cytoskeletal actin and intercellular proteins. The absence of dystrophin can lead to a failure of the exocytosis process, causing plasma membrane instability, muscle hypercontraction and ultimately muscle fibre degeneration.

In Border Collies breed, the disease is caused by a lethal X-linked mutation c.2841delT.

This means that it is localized on the X chromosome. Since the genotype of males is composed of X and Y chromosomes, they can be healthy (unaffected by the mutation) or affected. The female genotype contains two X chromosomes, so females can be either healthy, carriers or affected. Female carriers usually do not show clinical signs but are able to pass the mutated allele to their offspring. Related females of affected males should be tested to identify carriers. Breeding of female carriers is not recommended. A 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:

Mata López, S., Hammond, J.J., Rigsby, M.B., Balog-Alvarez, C.J., Kornegay, J.N., Nghiem, P.P. : A novel canine model for Duchenne muscular dystrophy (DMD): single nucleotide deletion in DMD gene exon 20. Skelet Muscle 8:16, 2018. Pubmed reference: 29843823