Phenotypes Associated with This Genotype

Genotype
MGI:5578132

• Allelic Composition: Tg(Alb-PDGFC)#Jcam/0
• Genetic Background: involves: C57BL/6

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

liver/biliary system

abnormal liver morphology ( J:96979 , J:211984 )

• increase in the deposition of collagen in the liver that is first seen at 2 weeks of age and is more prominent at 4-6 weeks of age; sinusoidal spaces show pericellular deposition of fibrillar collagen, with a 2-5 fold increase in collagen deposition (J:96979)

• livers show various abnormalities including unilocular or multiocular pseudocysts without epithelial lining, angiogenesis, dysplastic foci or foci of altered hepatocytes by 6-7 months of age, and preneoplastic foci in all mice by 12 months of age (J:96979)

• low level of liver injury as indicated by an increase in circulating IL-6 (J:211984)

abnormal liver vasculature morphology ( J:211984 )

• mice show extensive vascular changes and venous malformations in the liver

• as early as 10 months of age, gross venous malformations are seen on the surface of livers, indicative of neoangiogenesis

abnormal liver sinusoid morphology ( J:96979 , J:211984 )

• an increase in the numbers of sinusoidal lining cells that is first seen by 2 weeks of age and is more prominent at 4-6 weeks of age (J:96979)

• at 6 weeks of age, an increase in collagen deposition is seen within the sinusoids and radiating form the central veins (J:96979)

• congested sinusoids with extensive extracellular matrix deposition (J:211984)

liver vascular congestion ( J:211984 )

• congested sinusoids with extensive extracellular matrix deposition and a lack of fenestrae, suggesting that capillarization occurs

enlarged liver ( J:96979 )

• aged mice show enlarged liver, with liver weight:body weight ratios of 50-75% greater than in wild-type mice

abnormal Ito cell morphology ( J:96979 )

• activation of hepatic stellate cells as indicated by increased replication of perisinusoidal cells and alpha-SMA and GFAP expression

hepatic steatosis ( J:96979 )

• thin tracts of collagen surround areas of micro- and macrovesicular steatosis

• however, regenerating nodules or classic cirrhosis is not seen

macrovesicular hepatic steatosis ( J:96979 )

microvesicular hepatic steatosis ( J:96979 )

increased hepatocellular carcinoma incidence ( J:96979 , J:211984 )

• about 80% of mice develop hepatocellular carcinoma by 1 year of age (J:96979)

• dysplastic foci are seen in 44% of livers at 4-5 months of age, 68% of livers at 8-9 months and in 100% of livers at 12 months (J:211984)

• 26% of mice have macroscopic liver tumors by 9 months and 85% by 12 months (J:211984)

liver fibrosis ( J:96979 , J:211984 )

• mice exhibit progressive development of hepatic fibrosis that becomes more severe with age such that by 13 weeks, mice show overt hepatic fibrosis that resembles human alcoholic or nonalcoholic fatty liver disease (J:96979)

abnormal liver physiology ( J:211984 )

• evidence of apoptosis in multiple cell types of the liver at 1.5 months of age

• presence of councilman bodies in the liver of 8 month old mice

increased hepatocyte proliferation ( J:96979 )

• hepatocyte DNA replication is 2-4 fold higher at 6 weeks of age

chronic liver inflammation ( J:211984 )

• focal inflammation that becomes more widespread with age and results in chronic inflammation

growth/size/body

enlarged liver ( J:96979 )

• aged mice show enlarged liver, with liver weight:body weight ratios of 50-75% greater than in wild-type mice

enlarged spleen ( J:211984 )

• all mice have splenomegaly

neoplasm

increased hepatocellular carcinoma incidence ( J:96979 , J:211984 )

• about 80% of mice develop hepatocellular carcinoma by 1 year of age (J:96979)

• dysplastic foci are seen in 44% of livers at 4-5 months of age, 68% of livers at 8-9 months and in 100% of livers at 12 months (J:211984)

• 26% of mice have macroscopic liver tumors by 9 months and 85% by 12 months (J:211984)

cardiovascular system

abnormal liver vasculature morphology ( J:211984 )

• mice show extensive vascular changes and venous malformations in the liver

• as early as 10 months of age, gross venous malformations are seen on the surface of livers, indicative of neoangiogenesis

abnormal liver sinusoid morphology ( J:96979 , J:211984 )

• an increase in the numbers of sinusoidal lining cells that is first seen by 2 weeks of age and is more prominent at 4-6 weeks of age (J:96979)

• at 6 weeks of age, an increase in collagen deposition is seen within the sinusoids and radiating form the central veins (J:96979)

• congested sinusoids with extensive extracellular matrix deposition (J:211984)

liver vascular congestion ( J:211984 )

• congested sinusoids with extensive extracellular matrix deposition and a lack of fenestrae, suggesting that capillarization occurs

abnormal vein morphology ( J:211984 )

• many mice exhibit grossly dilated mesenteric veins

hemoperitoneum ( J:211984 )

• cause of death is usually hemoperitoneum, with extensive blood and fluid in the peritoneal cavity

cellular

increased hepatocyte proliferation ( J:96979 )

• hepatocyte DNA replication is 2-4 fold higher at 6 weeks of age

homeostasis/metabolism

abnormal circulating protein level ( J:211984 )

• increase in circulating levels of vascular endothelial growth factor at 12 months of age

increased circulating interleukin-6 level ( J:211984 )

abnormal circulating enzyme level ( J:96979 )

• serum transaminase and alkaline phosphatase levels are mildly elevated at 9 months of age

• however, serum transaminase levels are normal up to 3 months of age

increased circulating alanine transaminase level ( J:211984 )

• at 12 months of age

increased circulating alkaline phosphatase level ( J:96979 , J:211984 )

• serum alkaline phosphatase levels are mildly elevated at 9 months of age (J:96979)

• at 12 months of age (J:211984)

increased circulating aspartate transaminase level ( J:211984 )

• at 12 months of age

hematopoietic system

enlarged spleen ( J:211984 )

• all mice have splenomegaly

immune system

enlarged spleen ( J:211984 )

• all mice have splenomegaly

increased circulating interleukin-6 level ( J:211984 )

chronic liver inflammation ( J:211984 )

• focal inflammation that becomes more widespread with age and results in chronic inflammation

mortality/aging

premature death ( J:211984 )

• medial survival of 16 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:211984
steatotic liver disease		DOID:9452	OMIM:228100	J:96979