Homozygous alpha-sarcoglycan targeted mutant mice develop a progressive pathology characteristic of limb-girdle muscular dystrophy type 2D starting at one week of age. Necrosis, regeneration, central nucleation, atrophy, hypertrophy, fiber splitting and endomysial fibrosis are observed in their muscle.
When combined with a human epsilon-sarcoglycan transgene driven by a mouse muscle creatine kinase promoter specific to skeletal and heart muscle (as in this compound mutant strain) mice display no overt phenotype with normal behavior and normal muscle force generation. After mild exercise, the compound mutants show an exaggerated fatigue response. Biochemically, the mice show normal levels of nNOS (NOS1) in muscle homogenates, but variable levels in membrane fractions. By immunofluorescence, nNOS (NOS1) is not localized to all muscle membrane fibers.
