Laminin alpha2 deficiency in two Great Dane dogs: clinical, histological and molecular insights

The congenital muscular dystrophies (CMDs) are a group of genetically and clinically heterogeneous hereditary myopathies, characterized by hypotonia and early onset of progressive muscle weakness associated with dystrophic pattern on muscle biopsy. The clinical course is variable and brain and eyes can be involved. We report the main clinical and diagnostic data concerning the CMD related to laminin alpha 2 deficiency observed in two Great Dane dogs. Two one-month-old Great Dane puppies, a male and a female, were referred because of quadriceps femoris contracture, which resulted in hyperextension of the pelvic limbs. In the male dog the contracture was bilateral associated with ocular malformation and neurological deficit signs, whereas, in the female only the left hindlimb was affected. Serological examination and PCR on blood and cerebral liquor samples were negative for Neospora canis and Toxoplasma gondii. EMG showed a reduced motor nerve conduction velocity and brain TC showed severe hydrocephalus in the male dog. Muscle biopsies of the quadriceps femoris showed, in both animals, dystrophic changes including variability of fiber size, marked endomysial fibrosis and perimysial lipid accumulation. Immunohistochemistry and Western blot analysis showed absence, in the male, and decrease, in the female, of laminin alpha 2 chain and normal expression of dystrophin and other dystrophin-associated glycoproteins complex. The pathological features described are similar to primary merosin (laminin alpha 2) deficiency in humans. This report is the first description of primary deficit of merosin in dog.