Mouse Genome Informatics
hm
    Cav3tm1Mls/Cav3tm1Mls
involves: 129/Sv * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Cav3tm1Mls/Cav3tm1Mls hearts display progressive left ventricular wall thickening

muscle
N
• skeletal muscle of males does not show increased tubular aggregate formation as seen in Cav1tm1Mls and Cav2tm1Mls mutants (J:117199)
• homozygotes show a selective loss of muscle caveolae in cardiac myocytes; notably, adjacent endothelial cells retain their non-muscle caveolae
• in addition, mutant cardiac myocytes display exclusion of the dystrophin-glycoprotein complex (alpha-sarcoglycan) from lipid raft microdomains/caveolae
• at 4 months, mutant hearts show a ~20% reduction in fractional shortening, consistent with chamber dilation and increased wall thickness
• notably, both diastolic and systolic blood pressures remain normal
• homozygotes develop a progressive, mild-to-moderate cardiomyopathy characterized by loss of cardiac myocyte caveolae and myocyte hypertrophy
• homozygotes display absence of caveolae at the sarcolemma; as expected, caveolae are still present in mutant endothelial cells
• homozygotes exhibit absence of sarcolemmal caveolae, and mutant skeletal muscle fibers display exclusion of the dystrophin-glycoprotein complex from cholesterol-sphingolipid raft microdomains/caveolae
• mutant skeletal muscle fibers display a disorganized, immature T-tubule system with dilated and longitudinally oriented T-tubules
• homozygotes exhibit variable skeletal muscle fiber size
• homozygotes exhibit presence of necrotic skeletal muscle fibers
• homozygotes display a mild-to-moderate muscular dystrophy phenotype, consistent with sporadic ~3-4-fold elevations in serum creatine kinase activity and skeletal muscle fiber degeneration noted in some muscle tissue sections
• homozygotes show mild myopathic changes in the absence of an overt clinical phenotype

cardiovascular system
• homozygotes show a selective loss of muscle caveolae in cardiac myocytes; notably, adjacent endothelial cells retain their non-muscle caveolae
• in addition, mutant cardiac myocytes display exclusion of the dystrophin-glycoprotein complex (alpha-sarcoglycan) from lipid raft microdomains/caveolae
• at 4 months, homozygotes show a ~20% in intraventricular septal thickness relative to wild-type mice
• at 2 months or later, mutant hearts exhibit hypertrophic cardiac myocytes with accompanying cellular infiltrates
• homozygotes show a progressive and uniform increase in left ventricular wall diameter from 2 to 4 months, suggesting eccentric hypertrophy
• at 4 months, mutant hearts show a significant increase in left ventricular chamber diameter (~20% and ~50% during diastole and systole, respectively)
• at 4 months, mutant hearts display a notable increase in left ventricular chamber diameter during both diastole and systole, as compared with hearts at 2 months of age
• at 2 months, mutant hearts show a moderate increase (~10%) in left ventricular wall thickness during diastole
• by 4 months, left ventricular wall thickness is increased by ~20%, indicating progressive cardiomyopathy
• at 11 months, homozygotes exhibit increased interstitial/peri-vascular fibrosis at the junction of the right and left ventricles; no ischemia is observed
• at 4 months, mutant hearts show a ~20% reduction in fractional shortening, consistent with chamber dilation and increased wall thickness
• notably, both diastolic and systolic blood pressures remain normal
• homozygotes develop a progressive, mild-to-moderate cardiomyopathy characterized by loss of cardiac myocyte caveolae and myocyte hypertrophy

cellular
• homozygotes display absence of caveolae at the sarcolemma; as expected, caveolae are still present in mutant endothelial cells

homeostasis/metabolism
• at 11 months, homozygotes exhibit increased interstitial/peri-vascular fibrosis at the junction of the right and left ventricles; no ischemia is observed
• sporadic ~3-4-fold elevations in serum creatine kinase activity

Mouse Models of Human Disease
OMIM IDRef(s)
Muscular Dystrophy, Limb-Girdle, Type 1C; LGMD1C 607801 J:69965