Figure 2. Biochemical and Physiological Skeletal-Muscle Phenotypes of Disease in Gene-Targeted Mice with the Same Dystroglycan Mutation as the Patient.

Panel A shows immunofluorescence and histologic analyses of T190→M skeletal-muscle (iliopsoas) sections prepared when the animals were 21 weeks of age. Serial sections were stained with antibodies against glycosylated α-dystroglycan (IIH6), the α-dystroglycan core (CORE), and β-dystroglycan (β-DG). Histologic abnormalities in the sections were evaluated by means of hematoxylin and eosin (H and E) staining. White arrowheads indicate centrally nucleated fibers (scale bar, 50 μm). Panel B shows a representative biochemical analysis of wild-type (WT) and T190→M α-dystroglycan isolated from wheat-germ agglutinin–enriched homogenates of skeletal muscle. Both Western blotting and laminin-overlay assays were carried out. Functional modification of α-dystroglycan was impaired by the T190→M mutation in vivo, as shown by the dramatic reduction in IIH6 immunoreactivity and laminin binding in the absence of major differences in CORE and β-DG immunoreactivity. Panel C shows the uptake of Evans blue dye in the diaphragm after exercise in wild-type and T190→M mice at 8 weeks of age. Panel D shows the whole-mouse grip-strength measurements, in gram-force (g–F), for the T190→M mice and their wild-type littermates. The P value was obtained with the use of Student’s t-test.