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Phenotypes Associated with This Genotype
Genotype
MGI:5702658
Allelic
Composition
Ptentm2Mak/Ptentm2Mak
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm2Mak mutation (4 available); any Pten mutation (78 available)
Speer6-ps1Tg(Alb-cre)21Mgn mutation (6 available); any Speer6-ps1 mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• liver is larger in 10 week old mice and further enlarged at 40 weeks
• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks

liver/biliary system
• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age
• increase in hepatocyte proliferation at 10 weeks of age
• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age
• liver is larger in 10 week old mice and further enlarged at 40 weeks
• liver weight per body weight ratio is increased 2-fold at 10 weeks and 3-fold at 40 weeks
• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen
• hepatocytes acquire expression of an adipocyte-specific marker
• Mallory bodies are frequently seen in hepatocytes by 40 weeks of age
• absolute numbers of total liver cells are almost normal at 10 weeks of age but increased by 1.5-fold at 40 weeks
• cytoplasm of liver cells is weakly eosinophilic and contains numerous microvesicular vacuoles containing lipids at 10 weeks of age; vacuolar changes are seen mainly around the central vein
• steatotic changes are more prominent in male than female mice
• by 40 weeks of age, livers show fatty changes of increased severity throughout the hepatic lobule such that aged liver resembles adipocytes in fat tissues
• however, no fibrotic changes are seen in the liver
• livers are light-colored at 10 weeks of age and homogenously white in color at 40 weeks
• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas
• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas

homeostasis/metabolism
• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• glucose levels are lower in fasted mutants both before and after oral glucose administration
• serum insulin levels are reduced at 12 weeks of age
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
• serum levels are elevated at 40 weeks of age but not at 10 weeks of age
• intraperitoneal insulin injection reduces glucose levels by a greater amount than in wild-type mice indicating insulin hypersensitivity
• 16-carbon monosaturated fatty acids (C16:1) and C18:1 fatty acids are increased in livers of 10 week old mice and C16:0, C16:1, C18:0, C18:1, and C18:2 fatty acids are increased in livers of 40 week old mice
• triglyceride levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• however, no differences in liver levels of free fatty acids, free cholesterol, or phospholipids are seen

neoplasm
• hepatocellular carcinomas are seen in 5 of 6 males and 3 of 6 females; the hepatocellular carcinomas develop within liver adenomas and contain many fewer cytoplasmic lipid droplets than the adenomas
• macroscopic hepatic tumors are present in 66% of male and 30% of female mice at 40-44 weeks of age; nodular lesions resemble liver adenomas and cells with large droplets in the cytoplasm are prominent in most adenomas
• 2 mutants with hepatocellular carcinoma show lung metastasis

cardiovascular system
• mild sinusoidal fibrogenic changes and accumulations of lobular inflammatory cells are seen by 40 weeks of age

cellular
• increase in hepatocyte proliferation at 10 weeks of age
• however, no differences in hepatocyte apoptosis are seen at 10 or 40 weeks of age
• cholesterol ester levels are increased in the liver at 10 weeks of age and are highly elevated at 40 weeks of age
• hepatic hydrogen peroxide levels in the liver are increased 7-fold, indicating increased production of reactive oxygen species


Contributing Projects:
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
01/18/2022
MGI 6.17
The Jackson Laboratory