Phenotypes Associated with This Genotype

Genotype
MGI:2660653

• Allelic Composition: Cav3^tm1Mls/Cav3^tm1Mls
• Genetic Background: involves: 129/Sv * C57BL/6J * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Cav3^tm1Mls/Cav3^tm1Mls hearts display progressive left ventricular wall thickening

growth/size/body

cardiac hypertrophy ( J:79453 )

• at 2 months or later, mutant hearts exhibit hypertrophic cardiac myocytes with accompanying cellular infiltrates

heart left ventricle hypertrophy ( J:79453 )

• homozygotes show a progressive and uniform increase in left ventricular wall diameter from 2 to 4 months, suggesting eccentric hypertrophy

muscle

muscle phenotype ( J:117199 )

N • skeletal muscle of males does not show increased tubular aggregate formation as seen in Cav1^tm1Mls and Cav2^tm1Mls mutants

abnormal myocardial fiber morphology ( J:79453 )

• 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

heart left ventricle hypertrophy ( J:79453 )

• homozygotes show a progressive and uniform increase in left ventricular wall diameter from 2 to 4 months, suggesting eccentric hypertrophy

decreased heart ventricle muscle contractility ( J:79453 )

• 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

cardiomyopathy ( J:79453 )

• homozygotes develop a progressive, mild-to-moderate cardiomyopathy characterized by loss of cardiac myocyte caveolae and myocyte hypertrophy

abnormal sarcolemma morphology ( J:69965 )

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

abnormal skeletal muscle fiber morphology ( J:69965 )

• 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

increased variability of skeletal muscle fiber size ( J:69965 )

• homozygotes exhibit variable skeletal muscle fiber size

skeletal muscle fiber necrosis ( J:69965 )

• homozygotes exhibit presence of necrotic skeletal muscle fibers

dystrophic muscle ( J:69965 )

• 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

myopathy ( J:69965 )

• homozygotes show mild myopathic changes in the absence of an overt clinical phenotype

cardiovascular system

abnormal myocardial fiber morphology ( J:79453 )

• 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

thick interventricular septum ( J:79453 )

• at 4 months, homozygotes show a ~20% in intraventricular septal thickness relative to wild-type mice

cardiac hypertrophy ( J:79453 )

• at 2 months or later, mutant hearts exhibit hypertrophic cardiac myocytes with accompanying cellular infiltrates

heart left ventricle hypertrophy ( J:79453 )

• homozygotes show a progressive and uniform increase in left ventricular wall diameter from 2 to 4 months, suggesting eccentric hypertrophy

increased heart left ventricle wall thickness ( J:79453 )

• 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

dilated heart left ventricle ( J:79453 )

• 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

cardiac fibrosis ( J:79453 )

• at 11 months, homozygotes exhibit increased interstitial/peri-vascular fibrosis at the junction of the right and left ventricles; no ischemia is observed

decreased heart ventricle muscle contractility ( J:79453 )

• 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

cardiomyopathy ( J:79453 )

• homozygotes develop a progressive, mild-to-moderate cardiomyopathy characterized by loss of cardiac myocyte caveolae and myocyte hypertrophy

cellular

absent caveolae ( J:79453 )

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

homeostasis/metabolism

increased circulating creatine kinase level ( J:69965 )

• sporadic ~3-4-fold elevations in serum creatine kinase activity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rippling muscle disease 2		DOID:0060255	OMIM:606072	J:69965