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PMID:11884617
| Citation |
Razani, B, Wang, XB, Engelman, JA, Battista, M, Lagaud, G, Zhang, XL, Kneitz, B, Hou, H Jr, Christ, GJ, Edelmann, W and Lisanti, MP (2002) Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Mol. Cell. Biol. 22:2329-44 |
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| Abstract |
Caveolin-2 is a member of the caveolin gene family with no known function. Although caveolin-2 is coexpressed and heterooligomerizes with caveolin-1 in many cell types (most notably adipocytes and endothelial cells), caveolin-2 has traditionally been considered the dispensable structural partner of the widely studied caveolin-1. We now directly address the functional significance of caveolin-2 by genetically targeting the caveolin-2 locus (Cav-2) in mice. In the absence of caveolin-2 protein expression, caveolae still form and caveolin-1 maintains its localization in plasma membrane caveolae, although in certain tissues caveolin-1 is partially destabilized and shows modestly diminished protein levels. Despite an intact caveolar membrane system, the Cav-2-null lung parenchyma shows hypercellularity, with thickened alveolar septa and an increase in the number of endothelial cells. As a result of these pathological changes, these Cav-2-null mice are markedly exercise intolerant. Interestingly, these Cav-2-null phenotypes are identical to the ones we and others have recently reported for Cav-1-null mice. As caveolin-2 expression is also severely reduced in Cav-1-null mice, we conclude that caveolin-2 deficiency is the clear culprit in this lung disorder. Our analysis of several different phenotypes observed in caveolin-1-deficient mice (i.e., abnormal vascular responses and altered lipid homeostasis) reveals that Cav-2-null mice do not show any of these other phenotypes, indicating a selective role for caveolin-2 in lung function. Taken together, our data show for the first time a specific role for caveolin-2 in mammalian physiology independent of caveolin-1. |
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| Keywords |
Adipose Tissue/cytology; Adipose Tissue/metabolism; Adipose Tissue/ultrastructure; Animals; Aorta/drug effects; Aorta/physiology; Body Weight; Caveolae/chemistry; Caveolae/metabolism; Caveolae/ultrastructure; Caveolin 1; Caveolin 2; Caveolins/deficiency; Caveolins/genetics; Caveolins/metabolism; Exercise Tolerance/genetics; Exercise Tolerance/physiology; Fasting/metabolism; Female; Lung/metabolism; Lung/pathology; Lung/physiopathology; Lung/ultrastructure; Male; Mice; Mice, Knockout; Microscopy, Fluorescence; Mutagenesis, Site-Directed; Nitric Oxide/pharmacology; Postprandial Period |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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