All Phenotypes Sart1<Gt(IST11321E11)Tigm> MGI Mouse

abnormal Kupffer cell morphology ( J:241191 )

• Kupffer cell hyperplasia in 6 of 6 livers at 14-18 months of age

enlarged liver ( J:241191 )

increased liver weight ( J:241191 )

• increase in average liver weight to body weight ratios

microvesicular hepatic steatosis ( J:241191 )

• mild to moderate microvesicular hepatic steatosis with increased severity in the lobular/periacinar and midzonal regions in males at 6 months of age

increased liver tumor incidence ( J:241191 )

• liver tumors detected by MRI in 57% (4 of 7) males at age 16-18 months of age but not in males under 10 months of age

• preneoplastic foci composed of hypertrophic or cytomegalic hepatocytes showing increased proliferation are present at 6 months of age in males

• treatment with a CCL5-neutralizing antibody for 5 weeks suppressed the development of new liver nodules

increased hepatocellular carcinoma incidence ( J:241191 )

• in 83% of males (5 of 6) multifocal large liver tumors, confirmed to be hepatocellular carcinomas (HCC), are found at necropsy

• in males livers show hallmarks of NASH-driven hepatocellular carcinoma with steatosis, fibrosis, and foci of immune cell infiltration

• livers of age matched females show minimal steatosis and no malignant tumors

• at 10 months of age, HCC is detected in 5 of 12 mice and preneoplastic foci are seen in 83% of mice

liver fibrosis ( J:241191 )

• in males over 14 months of age with tumors

abnormal liver physiology ( J:241191 )

• Kupffer cells show higher levels of secreted cytokines with a 100% increase in CCL5 secretion in mice over 6 months of age

liver inflammation ( J:241191 )

• foci of immune cell infiltration in males over 14 months of age with tumors

abnormal hepatocyte physiology ( J:241191 )

• defects in fatty acid oxidation with an almost 4-fold decrease in the ability to utilize exogenous palmitate in hepatocytes from 4 month old mice

abnormal Kupffer cell morphology ( J:241191 )

• Kupffer cell hyperplasia in 6 of 6 livers at 14-18 months of age

increased neutrophil cell number ( J:241191 )

• 6-fold increase in Ly6G+ neutrophils in the livers of male mice at 6 months of age

• 3-fold increase in Ly6G+ neutrophils in the livers of male mice at 1 months of age

abnormal immune cell physiology ( J:241191 )

• elevated Hif1a expression in liver infiltrating immune cells

abnormal chemokine secretion ( J:241191 )

• 100% increase in CCL5 secretion in Kupffer cells in mice over 6 months of age

liver inflammation ( J:241191 )

• foci of immune cell infiltration in males over 14 months of age with tumors

decreased body size ( J:241191 )

• at over 14 months of age males are significantly smaller compared to wild-type controls

enlarged liver ( J:241191 )

increased liver weight ( J:241191 )

• increase in average liver weight to body weight ratios

increased circulating alanine transaminase level ( J:241191 )

• at 6 months of age

increased circulating alkaline phosphatase level ( J:241191 )

• at 6 months of age

increased circulating aspartate transaminase level ( J:241191 )

• at 6 months of age

ruffled hair ( J:241191 )

• in males at over 14 months of age

increased liver tumor incidence ( J:241191 )

• liver tumors detected by MRI in 57% (4 of 7) males at age 16-18 months of age but not in males under 10 months of age

• preneoplastic foci composed of hypertrophic or cytomegalic hepatocytes showing increased proliferation are present at 6 months of age in males

• treatment with a CCL5-neutralizing antibody for 5 weeks suppressed the development of new liver nodules

increased hepatocellular carcinoma incidence ( J:241191 )

• in 83% of males (5 of 6) multifocal large liver tumors, confirmed to be hepatocellular carcinomas (HCC), are found at necropsy

• in males livers show hallmarks of NASH-driven hepatocellular carcinoma with steatosis, fibrosis, and foci of immune cell infiltration

• livers of age matched females show minimal steatosis and no malignant tumors

• at 10 months of age, HCC is detected in 5 of 12 mice and preneoplastic foci are seen in 83% of mice

abnormal Kupffer cell morphology ( J:241191 )

• Kupffer cell hyperplasia in 6 of 6 livers at 14-18 months of age

abnormal Kupffer cell morphology ( J:241191 )

• Kupffer cell hyperplasia in 6 of 6 livers at 14-18 months of age

increased neutrophil cell number ( J:241191 )

• 6-fold increase in Ly6G+ neutrophils in the livers of male mice at 6 months of age

• 3-fold increase in Ly6G+ neutrophils in the livers of male mice at 1 months of age

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

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:241191

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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