Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(Alb1-cre)1Dlr transgene insertion 1, Derek LeRoith MGI:2176946 |
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| Summary |
21 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• although liver histology was generally normal, hepatocytes were smaller with a larger nuclear volume
• after 2 weeks of treatment with peroxisome proliferators, the expected hypertrophy did not occur except for a few hepatocytes in centrilobular regions
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• the highest mortality rates occur at 3 weeks of age
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• all mice die by 7 weeks with the highest mortality rates at 3 weeks of age
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• at 3 weeks of age, mice exhibit hepatocyte apoptosis not observed in either single mutants or wild-type mice
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• at 3 weeks of age, mice exhibit hepatocyte necrosis not observed in either single mutants or wild-type mice
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• at 3 weeks of age, mice exhibit liver degeneration not observed in either single mutants or wild-type mice
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• at 3 weeks of age
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• at 3 weeks of age, mice exhibit hepatocyte apoptosis not observed in either single mutants or wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• insulin-induced inhibition of hepatic glucose production with a euglycemic clamp is attenuated
• inhibition of hepatic glucose production by ICV infusion of insulin is attenuated
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• insulin-induced inhibition of hepatic glucose production with a euglycemic clamp is attenuated even more than in single knockouts for either Stat3 or Pdk1
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• glucose tolerance is impaired further compared to conditional single Pdk1-null mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all mutants die before 10 months of age
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• increase in branching of bile ducts in the liver
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• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma
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• increase in branching of bile ducts in the liver
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• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma
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• increase in liver size and weight due to fat accumulation in the liver
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• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma
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• increase in liver size and weight due to fat accumulation in the liver
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Igf1tm1Dlr/Igf1tm1Dlr Igfalstm1Yrb/Igfalstm1Yrb Tg(Alb1-cre)1Dlr/? mice exhibit reduced growth plate height
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• 30% reduction in total length by 2-3 weeks of age
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• reduced cortical bone thickness
• reduced trabecular bone volume and trabecular bone density
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• 20% shorter at 21 days of age and 12% shorter at 6 weeks of age
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• reduced 15 %
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• reduced 26%
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• tibial growth plate height reduced by 20%
• germinal zone height increased in the tibia
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• reduced cortical bone thickness
• reduced trabecular bone volume and trabecular bone density
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• 20% shorter at 21 days of age and 12% shorter at 6 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• insulin-induced inhibition of hepatic glucose production with a euglycemic clamp is attenuated
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• mice display an exaggerated increase in glucose concentration during a glucose-tolerance test
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• insulin levels are high compared to controls and other mutant lines
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 10 of 23 mutants between 2-11 months of age exhibit varying degrees of hyperplasia primarily in larger bile duct
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• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen
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• 10 of 23 mutants between 2-11 months of age exhibit varying degrees of hyperplasia primarily in larger bile duct
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• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen
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• 1 of 13 and 5 of 15 mutants develop hepatocellular carcinoma at 8-9 months of age and 12-16 months of age, respectively
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• 6 of 15 mutants between 12-16 months of age have cholangiocellular carcinoma foci, although much fewer of them and smaller ones than in double Smad4 and Pten mutants, and no invasive cholangiocelluar carcinomas were seen
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• 1 of 13 and 5 of 15 mutants develop hepatocellular carcinoma at 8-9 months of age and 12-16 months of age, respectively
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced lean mass at 8 weeks of age
• reduction in fraction of lean mass at 8 weeks of age
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• 12% and 20% smaller for female and male mice respectively, at 8 wk of age
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• reduced body length at 8 weeks of age
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• modest increase in body fat at 8 weeks of age
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• 60% decrease in circulating IGF-I level at 8 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• modest increase in body fat at 8 weeks of age
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• reduced lean mass at 8 weeks of age
• reduction in fraction of lean mass at 8 weeks of age
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• 12% and 20% smaller for female and male mice respectively, at 8 wk of age
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• reduced body length at 8 weeks of age
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• 60% decrease in circulating IGF-I level at 8 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• approximately 25% greater than control
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• in the fed state
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| N |
• food intake measured over 14 days was normal
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• in fed mutant mice
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• very high glucagon and glucagon-like peptide-1
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• in fed mutant mice
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• in fasted mutant mice
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• mutant mice had resting and total energy expenditure rate at 30 degree
• resting or total energy expenditure rate or activity level at ambient temperature are normal
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• increased glucose-stimulated insulin secretion
• increased insulin sensitivity in liver and muscle
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• in the fed state
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• reduced adiposity
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• alpha cell hyperplasia with les uniform cellular size and appearance
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• mutant mice had increased pancreas weights
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• mutant mice had increased pancreas weights
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• approximately 25% greater than control
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• beginning at 5 to 6 months of age
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• slightly after 8 months of age and in an insulin tolerance test
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• become significantly elevated
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• liver is histologically normal at 2 months but with some lipid droplet accumulation
• livers at 6 months were fat in about 56% of mice
• livers at 12 months were fat in about 78% of mice but only 17% of controls
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• serum levels become modestly elevated
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• becomes moderately elevated
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• become significantly elevated
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| steatotic liver disease | DOID:9452 |
OMIM:228100 |
J:179193 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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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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• 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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• unicellular necrosis of parenchymal cells at 5 weeks of age
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• male mutant LID (LID, chronic liver-specific IGF-1 deficiency) mice fed a high calorie or regular diet for 8 to 10 weeks exhibit decreased serum IGF-1 levels relative to controls
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• LID mice fed a high calorie for 8 to 10 weeks exhibit increased serum leptin levels compared to lean LID mice (fed a regular diet)
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• male double mutant (LID, chronic liver-specific IGF-1 deficiency) mice on a high calorie diet for 10-14 weeks and injected with subcutaneous MC-39 murine colorectal carcinoma cell do not show the obesity-associated increase in local tumor growth compared to lean controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• serum cholesterol levels are elevated by about 50%
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• serum triglyceride levels are significantly higher than in control mice
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• serum bile acids are greatly elevated in these mice
• total bile acid pool collected from liver, gallbladder and small intestine is significantly higher than in controls
• the increases in the bile acid pool consist of increases in cholate and its derivates including taurocholic acid and taurodeoxycholic acid
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adipocytes are smaller than in Cebpatm1Gonz Lepob homozygotes
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed a high carbohydrate diet
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• when fed a high carbohydrate diet, mice exhibit elevated serum glucose levels compared to similarly treated Cebpatm1Gonz Lepob homozygotes
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed regular chow
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed regular chow
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• hepatic glycogen content is higher than in Cebpatm1Gonz Lepob homozygotes
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• compared to similarly treated Cebpatm1Gonz Lepob homozygotes when fed regular chow
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• expression of genes involved in lipogenesis are decreased compared to in Cebpatm1Gonz Lepob homozygotes
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• when fed a high carbohydrate diet, mice exhibit a slight increase in serum VLDL compared to in similarly treated Cebpatm1Gonz Lepob homozygotes
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed regular chow
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed a high carbohydrate diet
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed a high carbohydrate diet
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed regular chow
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• when fed a high carbohydrate diet, mice exhibit a 47% lower hepatic cholesterol level compared to Cebpatm1Gonz Lepob homozygotes
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• hepatic triglyceride levels are lower than in Cebpatm1Gonz Lepob homozygotes
• when fed a high carbohydrate diet, mice exhibit a 46% lower hepatic triglyceride level compared to Cebpatm1Gonz Lepob homozygotes
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• hepatic glycogen content is higher than in Cebpatm1Gonz Lepob homozygotes
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• when fed a high carbohydrate diet, mice exhibit a 47% lower hepatic cholesterol level compared to Cebpatm1Gonz Lepob homozygotes
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• hepatic triglyceride levels are lower than in Cebpatm1Gonz Lepob homozygotes
• when fed a high carbohydrate diet, mice exhibit a 46% lower hepatic triglyceride level compared to Cebpatm1Gonz Lepob homozygotes
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• mice are resistant to high carbohydrate diet induced steatosis
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• compared to in similarly treated Cebpatm1Gonz Lepob homozygotes when fed a high carbohydrate diet
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• when fed normal chow or a high carbohydrate diet
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by 8 weeks of age mortality is over 70%
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• at 5 weeks of age, mice begin to lose weight
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• sera levels are dramatically reduced relative to controls
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• sera levels are dramatically reduced relative to controls
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• sera levels are dramatically reduced relative to controls
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• liver has a gray, mottled appearance; marked pathological lesions are evident
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• hepatocytes are markedly vacuolated with material in vacuoles staining positive for fat; centrolobular hepatocytes are invariably hypertrophic with pale eosinophilic cytoplasmic inclusions
• most hepatocytes have large mitochondria and abundant lipid droplets while others both had lipid droplets and abundant glycogen-like material
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice develop normally, are healthy and fertile, and liver function appears normal
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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 12/10/2024 MGI 6.24 |
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