title: Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae.
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.
authors.affiliation: Department of Molecular Pharmacology, Institute for Smooth Muscle Biology, The Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Babak
authors.initials: B
authors.lastname: Razani
authors.forename: Xiao Bo
authors.initials: XB
authors.lastname: Wang
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Engelman
authors.forename: Michela
authors.initials: M
authors.lastname: Battista
authors.forename: Guy
authors.initials: G
authors.lastname: Lagaud
authors.forename: Xiao Lan
authors.initials: XL
authors.lastname: Zhang
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
authors.forename: Harry
authors.initials: H
authors.lastname: Hou
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
authors.forename: Winfried
authors.initials: W
authors.lastname: Edelmann
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D021941:Caveolae / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D017079:Exercise Tolerance / Q000235:genetics / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D005260:Female; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009569:Nitric Oxide / Q000494:pharmacology; D019518:Postprandial Period
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D009569:Nitric Oxide