Analysis Tools
normal phenotype
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• homozygotes are viable and exhibit no alterations in growth curves or metabolic parameters, such as plasma lipid and glucose levels, relative to wild-type controls
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Allele Symbol Allele Name Allele ID |
Hmgcrtm2Ishi targeted mutation 2, Shun Ishibashi MGI:5662445 |
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| Summary |
2 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes are viable and exhibit no alterations in growth curves or metabolic parameters, such as plasma lipid and glucose levels, relative to wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• unicellular necrosis of parenchymal cells at 5 weeks of age
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• ~30% of females survive until 12 months of age
• the survival rate of females is significantly higher than that of males
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• although born at a normal Mendelian frequency, 96% of males die with a median survival time of 35 days, whereas 71% of females die with a median survival time of 36 days
• no death occurs until 40 days of age in mice supplemented with mevalonate
• glucose supplementation dramatically improves the mortality of both sexes (96% versus 13% in males, and 71% versus 15% in females), indicating that hypoglycemia is the direct cause of lethality
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• although body weight is normal at 3 weeks of age, it decreases by 10% at 4 weeks and by 38% at 5 weeks of age
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• at 5 weeks of age, livers are enlarged
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• although liver weight is normal, the ratio of liver weight to body weight is increased by 39% and 74% at 4 and 5 weeks of age, respectively
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• unicellular necrosis of parenchymal cells at 5 weeks of age
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• at 5 weeks of age, livers are enlarged
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• although liver weight is normal, the ratio of liver weight to body weight is increased by 39% and 74% at 4 and 5 weeks of age, respectively
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• at 4 weeks of age, hepatic total cholesterol content is decreased by only 22%
• in culture, cholesterol synthesis in liver slices is reduced by 45%
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• at 4 weeks of age, hepatic triglyceride contents are increased 2-fold, indicating that neutral lipids stained with oil-red O in the liver are predominantly triglycerides
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• at 5 weeks of age, H&E staining showed moderate to severe ballooning and unicellular necrosis of liver parenchymal cells
• Oil-red O staining showed moderate to severe microvesicular steatosis of the parenchymal cells
• liver pathology is milder at 4 weeks than that at 5 weeks of age
• mice that survive the lethal period still exhibit hepatocyte ballooning
• liver pathology is almost completely reversed by supplementation with mevalonate
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• moderate to severe microvesicular steatosis of liver parenchymal cells at 5 weeks of age
• hepatic steatosis is completely reversed by providing mice with mevalonate
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• at 5 weeks of age, livers appear paler and whiter than control livers
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• at 5 weeks of age, TUNEL-positive and Ki-67-positive liver parenchymal cells are significantly increased 11- and 2.8-fold, respectively, relative to control mice
• caspase 3 activity in the liver is increased 1.8-fold at 5 weeks of age
• however, caspase 8 activity and hydrogen peroxide (H2O2) levels are not significantly altered
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• at 5 weeks of age
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• at 5 weeks of age, plasma levels of bilirubin are significantly increased
• the hyperbilirubinemia phenotype is normalized by supplementation with mevalonate
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• moderately hypoglycemic at 5 weeks of age
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• at 3 weeks of age, total cholesterol levels in the plasma are decreased by 26%
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• at 5 weeks of age, the plasma levels of total cholesterol and free cholesterol are increased 4.3-, 7.9-fold, respectively; in contrast, plasma cholesterol ester levels are decreased by 38%
• at 5 weeks of age, ratios of free cholesterol to cholesterol ester are increased 13-fold
• the hypercholesterolemia phenotype is almost normalized in mice supplemented with mevalonate
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• at 5 weeks of age, the plasma levels of phospholipids are increased 4.0-fold
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• plasma triglyceride levels are decreased by 69% and 70% at 4 and 5 weeks of age, respectively
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• at 5 weeks of age, agar gel electrophoresis of plasma revealed that both lipoprotein X and apoB-48-containing lipoproteins are increased
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• at 3 weeks of age, plasma concentrations of LDL cholesterol are decreased
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• at 5 weeks of age, most of the increased cholesterol is distributed in the size of very low-density lipoprotein through LDL
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• at 3 weeks of age, plasma concentrations of apolipoprotein (apo) B-100 protein are decreased
• at 5 weeks of age, apoB-100 levels remain decreased, whereas plasma apoB-48 levels are substantially increased
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• at 5 weeks of age, plasma levels of alanine transaminase are significantly increased
• ALT levels are almost normalized by supplementation with mevalonate
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• at 5 weeks of age, plasma levels of aspartate aminotransferase are significantly increased
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• at 4 weeks of age, hepatic total cholesterol content is decreased by only 22%
• in culture, cholesterol synthesis in liver slices is reduced by 45%
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• at 4 weeks of age, hepatic synthesis of fatty acids from acetate is markedly increased 17-fold
• fatty acid species C18:0, C18:1n-9, C20:1n-9, C20:3n-9, and C22:4n-6 are significantly increased in liver; however, total amount of fatty acids is not significantly altered
• hepatic levels of diglycerides are increased 1.8-fold, but those of ceramides are not significantly increased
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• at 5 weeks of age, plasma free fatty acid levels are increased 3.1-fold
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• at 4 weeks of age, the amounts of polyunsaturated fatty acids are increased in liver
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• at 4 weeks of age, hepatic triglyceride contents are increased 2-fold, indicating that neutral lipids stained with oil-red O in the liver are predominantly triglycerides
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• at 5 weeks of age, increased amounts of type 4 collagen are noted in liver
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/30/2024 MGI 6.23 |
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