All Phenotypes Cav1<tm1Kur> MGI Mouse

increased susceptibility to induced morbidity/mortality ( J:112452 )

• during the first 72 hours after partial hepatectomy, male homozygotes display a survival index of only 22.4% versus 89.1% in wild-type controls; however, mortality of both groups is rather similar during the first 48 hrs after surgery

• partially hepatectomized male homozygotes exhibit significant mortality beyond 48 hrs (72%) whereas all wild-type controls that survive at 48 hrs progress to 72 hrs

• treatment with glucose decreases mortality such that the survival index of partially hepatectomized mutant mice at 72 hrs (80%) reaches values comparable to those of glucose-treated wild-type mice (73%)

abnormal vasoconstriction ( J:71760 )

• significantly impaired myogenic tone and stimulated contractility

increased vasodilation ( J:71760 )

• abnormal endothelium-dependent relaxation of aortic rings: complete relaxation in response to acetylcholine

cellular phenotype ( J:71760 )

N	• normal plasma membrane cholesterol-enriched rafts in terms of protein expression and lipid composition • normal GPI-anchored proteins • normal trancytosis of macromolecules through endothelial cells

absent caveolae ( J:71760 )

• complete absence of caveolae in the endothelial and epithelial cells of lung tissue

• in addition, loss of caveolae in the adipose tissue, diaphragm, kidney, and heart

increased lung endothelial cell proliferation ( J:71760 )

• uncontrolled proliferation of lung endothelial cells (lung hypercellularity)

decreased hepatocyte proliferation ( J:112452 )

• analysis of specific proteins of the cell cycle machinery known to be regulated during liver regeneration indicates that, at >48 hrs after partial hepatectomy, regenerating mutant hepatocytes display atypical cell activation and fail to advance through the cell division cycle

• notably, no caspase activity is noted in regenerating livers at 48 hrs after hepatectomy

• glucose feeding reestablishes hepatocyte survival and cell cycle progression in partially hepatectomized mutant mice

homeostasis/metabolism phenotype ( J:71760 )

N	• normal albumin concentration in cerebrospinal fluid, despite loss of caveolae from the capillary network • normal blood lipoprotein composition • normal cholesterol content of high-density lipoprotein

impaired exercise endurance ( J:71760 )

• early signs of exhaustion indicating reduced physical ability in a forced swimming stress

abnormal lipid level ( J:112452 )

• partially hepatectomized homozygotes are able to synthesize triacylglycerol to some extent, but fail to store these lipids efficiently in lipid droplets as shown by the absence of lipid droplets in regenerating hepatocytes at 48 hrs after surgery

• no significant differences between wild-type and mutant mice are observed in the serum or liver before partial hepatectomy

decreased liver triglyceride level ( J:112452 )

• at >48 hrs after partial hepatectomy, the level of triacylglycerol in liver homogenates is clearly reduced in mutant mice, while the serum levels of triacylglycerol are similar between wild-type and mutant mice

increased lung endothelial cell proliferation ( J:71760 )

• uncontrolled proliferation of lung endothelial cells (lung hypercellularity)

abnormal type II pneumocyte morphology ( J:71760 )

• severe hypertrophy of type II pneumocytes

pulmonary interstitial fibrosis ( J:71760 )

• accumulation of fibers in the alveolar interstitium

thick pulmonary interalveolar septum ( J:71760 )

• prominent thickening of lung alvaeolar septa caused by an uncontrolled proliferation of endothelial cells (lung hypercellularity) and fibrosis

decreased liver triglyceride level ( J:112452 )

• at >48 hrs after partial hepatectomy, the level of triacylglycerol in liver homogenates is clearly reduced in mutant mice, while the serum levels of triacylglycerol are similar between wild-type and mutant mice

abnormal liver physiology ( J:112452 )

• at 48 hrs after partial hepatectomy, lipid droplet accumulation is markedly reduced in the livers of mutant males, while wild-type hepatocytes accumulate enlarged lipid droplets in the cytosol

• after 48 hrs of partial hepatectomy, the mean volume of lipid droplets is only 7.7% of cellular volume in mutant mice relative to 32.6% in wild-type mice

decreased hepatocyte proliferation ( J:112452 )

• analysis of specific proteins of the cell cycle machinery known to be regulated during liver regeneration indicates that, at >48 hrs after partial hepatectomy, regenerating mutant hepatocytes display atypical cell activation and fail to advance through the cell division cycle

• notably, no caspase activity is noted in regenerating livers at 48 hrs after hepatectomy

• glucose feeding reestablishes hepatocyte survival and cell cycle progression in partially hepatectomized mutant mice

impaired liver regeneration ( J:112452 )

• male homozygotes display impaired liver regeneration and low survival after a partial hepatectomy

• at 72 hrs after partial hepatectomy, the regeneration index (liver-to-body mass ratio) of male mutants is 2.2%, which represents only 38.0% of the original weight, while that of wild-type controls is 3.1% representing 52.5% of the original weight

• partially hepatectomized homozygotes that die during the 36 to 72 hr period (78%) display an extremely low regeneration index of ~1.7%

• liver regeneration is rescued by glucose feeding, with glucose-fed homozygotes displaying a regeneration index of 2.32%, which similarly to the wild-type glucose-fed mice represents 39.3% of the original liver weight