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Phenotypes Associated with This Genotype
Genotype
MGI:5009546
Allelic
Composition
Ptpn11tm1Gsf/Ptpn11tm1Gsf
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptpn11tm1Gsf mutation (0 available); any Ptpn11 mutation (46 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
• aged mutants become leaner by 10.7% for males and 14.9% for females, with a significant decrease of their body weights at 1 year of age
• lobular architecture of the liver is distorted by the development of hyperplastic hepatocyte plates

homeostasis/metabolism
• serum levels of alanine aminotransferase are higher than in controls
• serum levels of aspartate aminotransferase are higher than in controls
• injection of a single dose of diethylnitrosamine (DEN) on P15 results in an increase in the number and size of (hepatocellular carcinoma) liver tumors in mutants compared to controls

immune system
• intraperitoneal LPS injection elicits a stronger liver damage response in mutants than in controls as indicated by higher serum alanine aminotransferase levels
• mutants show a 130% increase in spleen size 14 days after LPS challenge as compared to 98% increase in controls indicating increased systemic inflammatory response
• mutants show increased inflammatory cell infiltration into hepatic parenchyma after LPS challenge
• circulating IL-6 and TNFalpha levels are increased following LPS injection
• LPS stimulation of isolated hepatocytes results in increased IL-6 secretion by mutant hepatocytes compared to controls
• 93% of mutant livers contain areas with infiltrate of inflammatory cells, concentrating around the portal triads with extension into the parenchyma
• necrotic zones of livers are always associated with inflammatory cells, whereas inflammation is occasionally observed without necrosis
• 8 of 19 aged mutants develop focal microgranuloma consisting of mononuclear inflammatory cells

liver/biliary system
• 93% of mutant livers contain areas with infiltrate of inflammatory cells, concentrating around the portal triads with extension into the parenchyma
• necrotic zones of livers are always associated with inflammatory cells, whereas inflammation is occasionally observed without necrosis
• 8 of 19 aged mutants develop focal microgranuloma consisting of mononuclear inflammatory cells
• one or several foci of pallor are noticeable on the liver surface of 34% of analyzed mutants
• beginning at 5 months of age, regenerative foci are noticeable in the liver and nodular regenerative hyperplasia is seen from 8 months of age
• hepatic inflammation and necrosis, leading to nodular regenerative hyperplasia
• lobular architecture of the liver is distorted by the development of hyperplastic hepatocyte plates
• hepatic parenchyma shows regenerative hyperplasia, with 13 of 19 livers having nodule formation
• the space between hepatocytes is reduced inside the nodules
• massive hepatocyte degeneration is seen inside of or surrounding the hyperplastic nodules, in association with vacuoles containing eosinophilic material, but not in the liver parenchyma
• liver shows small focal areas as well as large areas of parenchymal necrosis, with necrosis observed in 47% of mutants
• liver shows small focal areas of parenchymal necrosis
• from 12-18 months of age, one or a few hepatocellular adenomas are frequently seen in mutants; tumors bulge from the liver surface, are often paler than the hepatic parenchyma, but sometimes darker or red when accompanied by bleeding
• tumors are unencapsulated, well delimited and show expanding masses of hepatocytes
• fibrosis is seen at the portal triads but not near the necrosis or into the parenchyma

neoplasm
• injection of a single dose of diethylnitrosamine (DEN) on P15 results in an increase in the number and size of (hepatocellular carcinoma) liver tumors in mutants compared to controls
• from 12-18 months of age, one or a few hepatocellular adenomas are frequently seen in mutants; tumors bulge from the liver surface, are often paler than the hepatic parenchyma, but sometimes darker or red when accompanied by bleeding
• tumors are unencapsulated, well delimited and show expanding masses of hepatocytes

cellular

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
hepatocellular adenoma DOID:0050868 J:172422


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
11/05/2024
MGI 6.24
The Jackson Laboratory