Caveolin-1/3 double-knockout XXXX are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype.

@entity32 @entity296 @entity82 @entity19 @entity1184 @entity1283 @entity5689 @entity3207 @entity70894 @entity15587 @entity3895 @entity14582
The caveolin gene family consists of caveolins 1, 2, and 3. @entity14582 are co-expressed in many cell types, such as endothelial cells, fibroblasts, smooth muscle cells and adipocytes, where they form a heteroligomeric complex. In contrast, the expression of @entity15587 is muscle-specific. Thus, the expression of @entity5689 is required for caveolae formation in non-muscle cells, while the expression of @entity15587 drives caveolae formation in striated muscle cell types (cardiac and skeletal). To create a truly caveolae-deficient @entity19 , we interbred @entity3895 -1 null @entity19 and @entity3895 -3 null @entity19 to generate @entity3895 -1/ @entity3895 -3 double-knockout ( @entity3895 -1/3 dKO) @entity19 . Here, we report that @entity3895 -1/3 dKO @entity19 are viable and fertile, despite the fact that they lack morphologically identifiable caveolae in endothelia, adipocytes, smooth muscle cells, skeletal muscle fibers, and cardiac myocytes. We also show that these @entity19 are deficient in all three caveolin gene products, as @entity70894 is unstable in the absence of @entity5689 . Interestingly, @entity3895 -1/3 dKO @entity19 develop a severe @entity296 . At 2 months of age, analysis of @entity3895 -1/3 dKO hearts via gated magnetic resonance imaging reveals a dramatic increase in left ventricular wall thickness, as compared with @entity3895 -1-KO, @entity3895 -3 KO, and wild-type @entity19 . Further functional analysis of @entity3895 -1/3 dKO hearts via transthoracic echocardiography demonstrates @entity1184 and dilation of the left ventricle, with a significant decrease in fractional @entity3207 . As predicted, Northern analysis of RNA derived from the left ventricle of @entity3895 -1/3 dKO @entity19 shows a dramatic up-regulation of the atrial natriuretic factor message, a well-established biochemical marker of @entity1283 . Finally, histological analysis of @entity3895 -1/3 dKO hearts reveals @entity1184 , disorganization, and degeneration of the cardiac myocytes, as well as chronic interstitial @entity82 and @entity32 . Thus, dual ablation of both @entity3895 -1 and @entity3895 -3 genes in @entity19 leads to a pleiotropic defect in caveolae formation and severe @entity296 .
