Some important phenotypes of Cav-1 and Cav-3–deficient mice. (a) A deficiency in Cav-1 is sufficient to completely disrupt caveolae formation. Tissues thus far examined include endothelial cells (8, 9), adipocytes (Razani and Lisanti, unpublished observations), and mouse embryonic fibroblasts (MEFs) (8). The transmission electron micrographs shown are from near-confluent MEFs (8). (b) Cav-1–deficient mice show lung abnormalities, with constricted alveolar spaces, thickened septa, and hyper-cellularity. One-micron sections of lung parenchyma were cut, stained with Toluidine-Blue, and images were acquired with a 60× objective. Left panel, wild-type mice (WT); Right panel, Cav-1–null mice (KO) (8). (c) Cav-1–deficient mice show hyper-responsiveness to endothelium/nitric oxide (NO)-dependent vasodilation. Note that acetylcholine (Ach)-induced relaxation (a NO-dependent phenomenon) of the Cav-1–null aortic rings was clearly potentiated by the loss of Cav-1 expression. Concentration-dependent relaxation induced by acetylcholine (Ach; expressed as log of molar concentration) in aortas pre-constricted with 10 μM phenylephrine (PE) from wild-type (WT; open squares) and Cav-1–null (KO; black squares) mice. ***P < 0.0001 vs. WT (8). (d) A deficiency in Cav-3 is sufficient to completely disrupt the formation of sarcolemmal caveolae. The transmission electron micrographs shown are from hindlimb skeletal muscle fibers imaged at 25,000× magnification (32). (e) Cav-3–deficient mice show skeletal muscle abnormalities, with variability in muscle fiber size, the presence of some necrotic fibers, and mononuclear infiltrates. Muscle tissue sections from wild-type (left panel) and Cav-3 KO mice (right panel) were cut and stained with hematoxylin and eosin (H&E). (f) Cav-3 protein expression is required for the development of a mature and highly organized T-tubule system. Cav-3 KO T-tubules are dilated and run in irregular directions. Skeletal muscle tissue samples from wild-type (left panel) and Cav-3 KO (right panel) were subjected to T-tubule system staining using potassium ferrocyanate, which gives T-tubules an electron-dense (black) appearance (32).