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Phenotypes Associated with This Genotype
Genotype
MGI:4829790
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (39 available)
Speer6-ps1Tg(Alb-cre)21Mgn mutation (5 available); any Speer6-ps1 mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
liver/biliary system
• progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age
• at 12 months of age, livers show increased cell proliferation
• progressive and chronic liver injury that begins before proliferation of hepatic progenitors
• accumulation of hepatic progenitor cells in the periductal region of livers from 9-12 months of age
• liver shows multiple layers of progenitor cells surrounding a single layer of ductal cells which show high mitotic activity after 9 months of age
• increase in glycogen storage in the liver
• 3-fold increase in triglyceride content in the liver (J:88441)
• however, normal levels of plasma triglycerides (J:88441)
• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively (J:160759)
• mutants exhibit elevated hepatic triglyceride levels (J:171445)
• mutants treated with rapamycin exhibit no differences in steatosis or triglyceride levels compared to vehicle-treated mutants, however the average hepatocyte cell size was reduced, thus reducing the liver:body weight (J:171445)
• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age (J:171445)
• mutants treated with rapamycin show reduced hepatocyte cell size, thus reducing the liver:body weight ratio (J:171445)
• progressive development of fatty liver (J:88441)
• mutants exhibit enlarged, whitish livers containing large fat vacuoles by 12 weeks of age (J:171445)
• mutants treated with rapamycin exhibit no differences in steatosis compared to vehicle-treated mutants (J:171445)
(J:218587)
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma
• mice develop liver tumors starting at approximately 8-9 months of age
• 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age
• tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma

adipose tissue
• 50% reduction in total body fat content

homeostasis/metabolism
• decrease in fasting glucose levels at 1 and 3 months of age, however at 6 months of age, when severe steatosis is seen, the fasting glucose level is similar to wild-type
• decrease in fasting plasma insulin levels at 3 and 6 months of age
• decrease in serum leptin levels at one month of age
• however eating behavior is normal
• serum alanine aminotransferase levels increase progressively, reaching 5-fold higher levels at 12 months of age
• increase in glucose clearance during an intraperitoneal glucose load
• increase in glycogen storage in the liver
• increase in insulin sensitivity in the liver
• hepatocyte fatty acid uptake by passive diffusion is increased by 20% compared to controls, however active transportation of fatty acid is not changed and thus total fatty acid uptake is not significantly altered
• rate of fatty acid synthesis is 2.5-fold higher in mutant livers than in controls
• 30% decrease in circulating free fatty acids
• 3-fold increase in triglyceride content in the liver (J:88441)
• however, normal levels of plasma triglycerides (J:88441)
• 2-4-fold increase of triglyceride content in the liver of 1 and 3 month old mutants, respectively (J:160759)
• mutants exhibit elevated hepatic triglyceride levels (J:171445)
• mutants treated with rapamycin exhibit no differences in steatosis or triglyceride levels compared to vehicle-treated mutants, however the average hepatocyte cell size was reduced, thus reducing the liver:body weight (J:171445)
• decrease in lipolysis rate

cellular
• progressive hepatocyte cell death as mice progress from steatosis to premalignancy, with massive hepatocyte death by 9 months of age
• at 12 months of age, livers show increased cell proliferation
• marker analysis indicates oxidative stress in the liver

neoplasm
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma
• mice develop liver tumors starting at approximately 8-9 months of age
• 50% of mice develop tumors between 9 and 12 months of age and 100% develop tumors by 12 months of age
• tumors show mixed cell characteristics, with tumors composed of colangiocytes, hepatocytes, and bi-lineage cells
• tumors show compact trabecular growth patterns and pseudoglandular structures of hepatocellular carcinoma and tubular features of cholangiocyte carcinoma


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
12/03/2019
MGI 6.14
The Jackson Laboratory