Phenotypes Associated with This Genotype

Genotype
MGI:3625731

cx2

• Allelic Composition: Cav1^tm1Mls/Cav1^tm1Mls; Cav3^tm1Mls/Cav3^tm1Mls
• Genetic Background: involves: 129/Sv * C57BL/6J * SJL

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

cellular

cardiac interstitial fibrosis ( J:77372 )

• at 2 months, double homozygotes show cardiac interstitial fibrosis

absent caveolae ( J:77372 )

• double homozygotes are viable and fertile but lack morphologically identifiable caveolae in endothelia, adipocytes, smooth muscle cells, skeletal muscle fibers, and cardiac myocytes (first "truly caveolae-deficient" mouse model)

• in addition, double homozygotes are deficient in all three caveolin gene family members (first "caveolin-less" mouse model)

growth/size/body

increased heart weight ( J:77372 )

• at 2 months, double homozygotes show a ~33% increase in heart to body weight ratios relative to wild-type mice

cardiac hypertrophy ( J:77372 )

• at 2 months, double homozygotes display concentric cardiac hypertrophy, with increases of ~34% in interventricular septal thickness, posterior wall thickness, and left ventricular wall thickness; no further changes are noted at 4 months

heart left ventricle hypertrophy ( J:77372 )

• at 2 months, double homozygotes exhibit significant left ventricular hypertrophy relative to wild-type mice; no further hypertrophy is noted at 4 months

• left ventricular hypertrophy is associated with a switch to fetal programming, as shown by anomalous up-regulation of atrial natriuretic peptide

cardiovascular system

abnormal myocardial fiber morphology ( J:77372 )

• at 2 months, double homozygotes display significant cardiac myocyte hypertrophy and disarray interspaced with areas of myocytolysis

myocardial fiber disarray ( J:77372 )

thick interventricular septum ( J:77372 )

• at 2 months of age, double homozygotes exhibit a ~34% increase in interventricular septal thickness relative to wild-type mice

increased heart weight ( J:77372 )

• at 2 months, double homozygotes show a ~33% increase in heart to body weight ratios relative to wild-type mice

cardiac hypertrophy ( J:77372 )

• at 2 months, double homozygotes display concentric cardiac hypertrophy, with increases of ~34% in interventricular septal thickness, posterior wall thickness, and left ventricular wall thickness; no further changes are noted at 4 months

heart left ventricle hypertrophy ( J:77372 )

• at 2 months, double homozygotes exhibit significant left ventricular hypertrophy relative to wild-type mice; no further hypertrophy is noted at 4 months

• left ventricular hypertrophy is associated with a switch to fetal programming, as shown by anomalous up-regulation of atrial natriuretic peptide

increased heart left ventricle wall thickness ( J:77372 )

• at 2 months, double homozygotes show a ~41% increase in left ventricular wall thickness relative to wild-type mice

• increase in left ventricular wall thickness exceeds that observed in either single homozygote, suggesting a synergistic effect

dilated heart left ventricle ( J:77372 )

• at 2 months, double homozygotes show significant left ventricular dilation relative to wild-type mice, as shown by increases in end-diastolic diameter (3.27 0.16 vs 2.71 0.13 mm) and end-systolic diameter (2.02 0.07 vs 1.12 0.13 mm); no further dilation is noted at 4 months

increased heart right ventricle wall thickness ( J:77372 )

• at 2 months, a notable increase is detected in right ventricular wall thickness

cardiac interstitial fibrosis ( J:77372 )

• at 2 months, double homozygotes show cardiac interstitial fibrosis

decreased heart left ventricle muscle contractility ( J:77372 )

• at 2 months, double homozygotes show a significant reduction in left ventricular fractional shortening relative to wild-type mice (38.33 2.57 vs. 58.65 5.48 mm); however, no further deterioration is noted at 4 months

• neither significant differences in heart rate nor obvious conduction defects or cardiac arrhythmias are observed

cardiomyopathy ( J:77372 )

• double homozygotes develop a severe cardiomyopathy with left ventricular hypertrophy and chamber dilation, as assessed by gross morphology, cardiac MRI, and transthoracic echocardiography

heart inflammation ( J:77372 )

• at 2 months, double homozygotes exhibit significant chronic cardiac inflammation characterized by increased cellular infiltrates and fibrosis

muscle

abnormal myocardial fiber morphology ( J:77372 )

• at 2 months, double homozygotes display significant cardiac myocyte hypertrophy and disarray interspaced with areas of myocytolysis

myocardial fiber disarray ( J:77372 )

heart left ventricle hypertrophy ( J:77372 )

• at 2 months, double homozygotes exhibit significant left ventricular hypertrophy relative to wild-type mice; no further hypertrophy is noted at 4 months

• left ventricular hypertrophy is associated with a switch to fetal programming, as shown by anomalous up-regulation of atrial natriuretic peptide

decreased heart left ventricle muscle contractility ( J:77372 )

• at 2 months, double homozygotes show a significant reduction in left ventricular fractional shortening relative to wild-type mice (38.33 2.57 vs. 58.65 5.48 mm); however, no further deterioration is noted at 4 months

• neither significant differences in heart rate nor obvious conduction defects or cardiac arrhythmias are observed

cardiomyopathy ( J:77372 )

• double homozygotes develop a severe cardiomyopathy with left ventricular hypertrophy and chamber dilation, as assessed by gross morphology, cardiac MRI, and transthoracic echocardiography

immune system

heart inflammation ( J:77372 )

• at 2 months, double homozygotes exhibit significant chronic cardiac inflammation characterized by increased cellular infiltrates and fibrosis