Phenotypes Associated with This Genotype

Genotype
MGI:7384742

• Allelic Composition: Ssu72^tm1Cwl/Ssu72^tm1Cwl; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: B6.Cg-Ssu72^tm1Cwl Speer6-ps1^{Tg(Alb-cre)21Mgn}

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

liver/biliary system

liver inflammation ( J:309624 )

• livers show inflammatory cell infiltration

• expansion of liver macrophages

• elevation of intrahepatic IL-1beta, IL-6, and TNF-alpha levels

abnormal liver morphology ( J:309624 )

• 12-month old mice show signs of liver disease, including fatty change, necrosis, inflammatory cell infiltration, and increased liver injury with impaired liver damage response

increased liver weight ( J:309624 )

• ratio of liver weight to body weight is slightly increased in 5-week-old mice

abnormal liver development ( J:309624 )

• hepatocytes show aberrant chromosome polyploidy during postnatal liver development

abnormal hepatocyte morphology ( J:309624 )

• primary hepatocytes show higher proportions of octoploid hepatocytes but almost no diploid hepatocytes after weaning compared to wild-type hepatocytes which show increased tetraploid and octoploid and lower diploid after weaning, indicating an increase of the hepatic polyploidy population

• the proportion of octoploid hepatocytes gradually increase with age to reach almost 60% at 10 weeks whereas fewer than 20% of octoploid hepatocytes are seen in wild-type mice at the same age

• however, hepatocytes are composed of predominately diploid, with some tetraploid, before weaning as in wild-type hepatocytes and primary mouse embryonic fibroblasts exhibit normal diploidy

• livers show a decrease in the proportion of binucleated hepatocytes starting at 5 weeks of age

• livers show an increase in the size of mononuclear hepatocytes at 10 weeks of age

• livers show cytomegalic hepatocytes and cytoplasmic vacuolization

increased hepatocyte karyomegaly ( J:309624 )

• livers show an increase in nuclear diameters of mononuclear hepatocytes at 10 weeks of age

abnormal Ito cell morphology ( J:309624 )

• increase in the appearance and expansion of activated hepatic stellate cells

hepatic necrosis ( J:309624 )

hepatic steatosis ( J:309624 )

• livers show extensive steatosis, with increased lipid deposition in the hepatocytes and hepatocyte ballooning, characteristic of nonalcoholic steatohepatitis

liver fibrosis ( J:309624 )

• fibrillar collagen initially seen around the portal veins gradually increases such that many livers are fibrotic at 5 and 10 weeks of age

abnormal hepatocyte physiology ( J:309624 )

• hepatocyte cell cycle is arrested at G2 phase and/or delayed in the G2 to mitosis transition, however aberrant polyploid hepatocytes are able to reenter the cell cycle despite the G2/M arrest

increased hepatocyte apoptosis ( J:309624 )

• increase in hepatocyte apoptosis, particularly at 5 weeks

increased hepatocyte proliferation ( J:309624 )

• 5-week-old mice show an increase in hepatocyte proliferation

cellular

increased hepatocyte karyomegaly ( J:309624 )

• livers show an increase in nuclear diameters of mononuclear hepatocytes at 10 weeks of age

increased hepatocyte apoptosis ( J:309624 )

• increase in hepatocyte apoptosis, particularly at 5 weeks

increased hepatocyte proliferation ( J:309624 )

• 5-week-old mice show an increase in hepatocyte proliferation

growth/size/body

increased liver weight ( J:309624 )

• ratio of liver weight to body weight is slightly increased in 5-week-old mice

homeostasis/metabolism

increased circulating alanine transaminase level ( J:309624 )

• alanine aminotransferase (ALT) levels are highly elevated after weaning (5, 10, 20, and 52 weeks of age) but not at 3 weeks of age

increased circulating aspartate transaminase level ( J:309624 )

• aspartate aminotransferase (AST) levels are highly elevated after weaning but not at 3 weeks of age

increased physiological sensitivity to xenobiotic ( J:309624 )

• mice show increased susceptibility to carbon tetracholoride-induced liver damage, showing more severe liver necrosis and fibrosis and higher ALT, AST, and apoptosis levels, and elevation of intrahepatic fibrogenic cytokines such as IL-6 and TNF-alpha

immune system

liver inflammation ( J:309624 )

• livers show inflammatory cell infiltration

• expansion of liver macrophages

• elevation of intrahepatic IL-1beta, IL-6, and TNF-alpha levels

neoplasm

neoplasm ( J:309624 )

N • hepatocellular carcinoma is not seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
liver disease		DOID:409		J:309624