Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae

Babak Razani, Xiao Bo Wang, Jeffery A. Engelman, Michela Battista, Guy Lagaud, Xiao Lan Zhang, Burkhard Kneitz, Harry Hou, George J. Christ, Winfried Edelmann, Michael P. Lisanti

Research output: Contribution to journalArticle

239 Scopus citations

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.

Original languageEnglish
Pages (from-to)2329-2344
Number of pages16
JournalMolecular and cellular biology
Volume22
Issue number7
DOIs
StatePublished - Mar 25 2002
Externally publishedYes

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    Razani, B., Wang, X. B., Engelman, J. A., Battista, M., Lagaud, G., Zhang, X. L., Kneitz, B., Hou, H., Christ, G. J., Edelmann, W., & Lisanti, M. P. (2002). Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Molecular and cellular biology, 22(7), 2329-2344. https://doi.org/10.1128/MCB.22.7.2329-2344.2002