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Phenotypes Associated with This Genotype
Genotype
MGI:5578132
Allelic
Composition
Tg(Alb-PDGFC)#Jcam/0
Genetic
Background
involves: C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.
phenotype observed in females
phenotype observed in males
N normal phenotype
liver/biliary system
• 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)
• 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
• 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)
• congested sinusoids with extensive extracellular matrix deposition and a lack of fenestrae, suggesting that capillarization occurs
• aged mice show enlarged liver, with liver weight:body weight ratios of 50-75% greater than in wild-type mice
• activation of hepatic stellate cells as indicated by increased replication of perisinusoidal cells and alpha-SMA and GFAP expression
• thin tracts of collagen surround areas of micro- and macrovesicular steatosis
• however, regenerating nodules or classic cirrhosis is not seen
• 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)
• 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)
• 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
• hepatocyte DNA replication is 2-4 fold higher at 6 weeks of age
• focal inflammation that becomes more widespread with age and results in chronic inflammation

growth/size/body
• aged mice show enlarged liver, with liver weight:body weight ratios of 50-75% greater than in wild-type mice
• all mice have splenomegaly

neoplasm
• 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
• 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
• 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)
• congested sinusoids with extensive extracellular matrix deposition and a lack of fenestrae, suggesting that capillarization occurs
• many mice exhibit grossly dilated mesenteric veins
• cause of death is usually hemoperitoneum, with extensive blood and fluid in the peritoneal cavity

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

homeostasis/metabolism
• increase in circulating levels of vascular endothelial growth factor at 12 months of age
• 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
• serum alkaline phosphatase levels are mildly elevated at 9 months of age (J:96979)
• at 12 months of age (J:211984)

hematopoietic system
• all mice have splenomegaly

immune system
• all mice have splenomegaly
• focal inflammation that becomes more widespread with age and results in chronic inflammation

mortality/aging
• medial survival of 16 months


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
01/12/2022
MGI 6.17
The Jackson Laboratory