Mouse Genome Informatics
hm
    Sgcbtm1Kcam/Sgcbtm1Kcam
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
muscle
• homozygotes develop significant cardiomyopathy with extensive regions of necrosis, similar to morphological changes noted in tissue infarcts
• homozygotes exhibit loss of the sarcoglycan-sarcospan complex, the dystroglycan complex, and epsilon-sarcoglycan in skeletal, cardiac, and smooth muscles
• homozygotes display loss of the sarcoglycan-sarcospan complex in vascular smooth muscles leading to vascular perturbation, exaggeration of the muscular dystrophy and initiation of cardiomyopathy
• at 9 weeks, homozygotes display uptake of Evans blue dye in various skeletal muscles, indicating compromised sarcolemma integrity
• as early as 4 weeks, homozygotes exhibit progressive dystrophic calcification in the calf, thigh, and diaphragm muscles
• as early as 4 weeks, homozygotes exhibit progressive dystrophic changes in calf, thigh, and diaphragm muscles including pronounced areas of focal necrosis, dystrophic calcification, endomysial fibrosis, massive fatty infiltration, extensive central nucleation, fiber splitting and hypertrophy
• consistent with severe muscular dystrophy, 13-16-wk-old homozygotes exhibit increased serum creatine kinase activity

cardiovascular system
• at 4 weeks, vessels of the mutant heart and diaphragm display a serrated contour, rather than the smoothly tapered vessel walls observed in wild-type mice
• homozygotes display loss of the sarcoglycan-sarcospan complex in vascular smooth muscles leading to vascular perturbation, exaggeration of the muscular dystrophy and initiation of cardiomyopathy
• homozygotes display numerous areas of vascular constrictions often associated with pre- and poststenotic aneurysms in the vasculature of diaphragm, heart, and kidneys
• vascular constrictions are detected prior to the onset of necrotic changes
• as early as 9 weeks, mutant hearts display small necrotic areas
• at 20 weeks, focal necrotic areas resembling ischemic-like lesions are observed throughout the right and left ventricles; however, active myocardial necrosis is less prominent at 30 weeks
• at 30 weeks, mutant hearts exhibit widespread areas of fibrosis
• homozygotes exhibit multiple pre- and poststenotic aneurysms in vessels of the diaphragm, heart, and kidneys
• homozygotes develop significant cardiomyopathy with extensive regions of necrosis, similar to morphological changes noted in tissue infarcts

homeostasis/metabolism
• at 30 weeks, mutant hearts exhibit widespread areas of fibrosis

Mouse Models of Human Disease
OMIM IDRef(s)
Muscular Dystrophy, Limb-Girdle, Type 2E; LGMD2E 604286 J:60154