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Molecular and Cellular Biology, April 2002, p. 2329-2344, Vol. 22, No. 7
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.7.2329-2344.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Caveolin-2-Deficient Mice Show Evidence of Severe Pulmonary Dysfunction without Disruption of Caveolae

Babak Razani,1,2 Xiao Bo Wang,1,2 Jeffery A. Engelman,1,2 Michela Battista,1,2 Guy Lagaud,3 Xiao Lan Zhang,1,2 Burkhard Kneitz,4 Harry Hou, Jr.,4 George J. Christ,3 Winfried Edelmann,4 and Michael P. Lisanti1,2*

Department of Molecular Pharmacology,1 Departments of Urology, Physiology, and Biophysics, Institute for Smooth Muscle Biology ,3 Department of Cell Biology and The Albert Einstein Cancer Center, Albert Einstein College of Medicine,4 Division of Hormone-Dependent Tumor Biology, The Albert Einstein Cancer Center, Bronx, New York 104612

Received 24 October 2001/ Returned for modification 16 November 2001/ Accepted 11 December 2001

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.

* Corresponding author. Mailing address: Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-8828. Fax: (718) 430-8830. E-mail: lisanti{at}aecom.yu.edu.

Molecular and Cellular Biology, April 2002, p. 2329-2344, Vol. 22, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.7.2329-2344.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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