Muscular dystrophy in Golder Retriever (GRMD)

GRMD is a degenerative muscular disease causing loss of active muscular tissue and movement disorders. The disease is specific to the Golden Retriever breed.  The homologues of this disease have been identified in several animals including dogs, cats, mice, fish and some invertebrates. In humans, this syndrome is known as Duchenne´s muscular dystrophy (DMD).

The disease is characterized by deficiency of dystrophin in skeletal muscles caused by mutation in DMD gene. The dystrophin is a cytoskeletal protein that is present in particular in smooth, cardiac and skeletal muscles and in neurones in specific areas of the central nervous system.

Typical clinical signs of the muscular dystrophy include muscle weakness, impaired walking or swallowing and breathing difficulty. The disease is progressive and very often ends with death.  The affected dogs show muscle atrophy, elevated levels of serum creatine kinase, degeneration and mineralization of hyaline myofibrils, muscular fibrosis with fat infiltrations and cardiomyopathy. GRMD is usually expressed in puppies around 8 weeks of age. Dogs with severe form of the disease die soon after diagnosis, while dogs with milder form of the disease can survive several years.

GRMD is X-linked recessive disease. Disease is caused by c.531-2A>G mutation in DMD gene.

Inheritance of X-linked disease

Females have XX chromosomes. So females have three possibilities as regards GRMD disease:

• XnXn - females with two normal X chromosomes = normal phenotype, a healthy female
• XnXm - females with one normal X (Xn) and one mutant X (Xm) = a female carrier.
• XmXm - females with two mutated X chromosomes = an affected female

Males have XY chromosomes. So they have two possibilities as regards GRMD disease:

• XnY - normal phenotype, a healthy male
• XmY - an affected male; he inherited mutated X chromosome from his mother

Note:  Males are never X-linked disease carriers!

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By mating healthy male and carrier female, following offspring could be expected:

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As you can see in the table, by mating healthy male and carrier female, half of the male offspring will be GRMD affected and half of the female offspring will transfer GRMD to the next generations.

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References:

Lima et al: Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers; Growth Hormone & IGF Research 17 (2007) 480–491