Table 1.
Selected phenotypes of caveolin-1 knockout mice
| Organ system and phenotype | Proposed mechanism |
|---|---|
| Cancer | |
| Increased sensitivity to carcinogens | Increased cyclin D1 and ERK 1/2 levels |
| Delayed prostate tumour progression | Tumour suppression activity |
| Cardiac | |
| Cardiac hypertrophy | p42/44 MAP kinase hyperactivation |
| Dilated cardiomyopathy | Unknown |
| Central nervous system | |
| Reduced brain weight; multiple motor and behavioural abnormalities | Altered maintenance of cortico-striato-pallido-thalamo-pontine pathways involved in motor control |
| Endocrine-metabolic | |
| Adipocyte abnormalities with impaired lipolytic activity and altered lipid droplet architecture | Altered lipid homeostasis; altered perilipin phosphorylation |
| Accelerated mammary gland development | Hyperactivation of prolactin signaling |
| Decreased glucose uptake | Insulin resistance and altered glucose transporter localization |
| Gastrointestinal | |
| Hyperproliferation of intestinal crypt cells | Upregulation of Wnt/β-catenin signaling |
| Reduced nitric oxide-mediated intestinal smooth muscle relaxation | Abnormalities in interstitial cells of Cajal and smooth muscle |
| Decreased liver regeneration posthepatectomy | Impaired coordination of lipid metabolism and cell proliferation |
| Lymphoreticular | |
| Reduced response to thymus-independent antigens | Unknown |
| Pulmonary | |
| Constricted alveolar spaces | Thickened alveolar wall |
| Pulmonary hypertension | Multiple causes |
| Transport | |
| Disruption of glycosylphosphatidyl inositol-anchored protein transport | Altered Golgi protein processing |
| Urogenital | |
| Impaired renal calcium absorption | Abnormal function of plasma membrane calcium ATPase |
| Enlarged seminal vesicles | Engorgement of seminal fluid |
| Bladder hypertrophy | Smooth muscle hyperplasia |
| Vascular | |
| Reduced aortic contractile tone | Increase in endothelial nitric oxide activity |
| Impaired angiogenic response | Altered VEGF protein interactions |
| Neointimal hyperplasia | Increased cyclin D1 and ERK 1/2 levels |
| Microvascular permeability | Altered clefts and tight junctions |
| Abnormal arterial remodeling during changes in flow | Altered mechanotransduction |
Abbreviations: ERK, extracellular signal-regulated kinase; MAP, mitogen-activated protein; VEGF, vascular endothelial growth factor.