Mouse Genome Informatics
cx1
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/0
Tg(MtTGFA)42Lmb/0

involves: C57BL/6 * CBA * CD-1
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• three weeks after zinc administration through drinking water, the first signs of hepatic neoplasia are evident with large hepatocytes with compact nuclei being found around blood vessels
• after six weeks of zinc administration, 80% of mice display these neoplastic lesions
• after ten weeks of zinc administration, foci of dysplastic cells are found throughout the liver nodule
• intravascular spread of tumor cells is also observed ten weeks after zinc administration
• after 16 weeks of zinc administration, over 70% of mice carry single or multifocal nodules of which one quarter consist of well differentiated hepatocellular carcinomas displaying pseudoglandular or trabecular pattern
• the appearance of preneoplastic and neoplastic lesions also occur in mice with a delay of 6 to 8 weeks in mice not receiving zinc treatment


Mouse Genome Informatics
cx2
    Gtf2ird1Tg(Alb1-Myc)166.8Sst/Gtf2ird1+
Tg(MtTGFA)42Lmb/0

involves: C57BL/6 * CBA * CD-1
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
liver/biliary system
• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice
• most mice by 2 months of age have extensive dysplastic changes in the liver ranging from moderate cellular pleomorphism and hypertrophy to more advanced poly morphisms with severe cytomegaly and karyomegaly
• hepatocytes often display abnormal nuclear structures (tripolar mitosis, chromosome bridges, aberrant chromosomal migration, intranuclear lipid droplets, and nuclear eosinophilic pseudoinclusions)
• these dysplastic changes started in the perivascular areas of the liver, are most advanced around the central veins and are spreading throughout the hepatic lobe
• metastasis to the lung and spleen is observed only rarely
• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins
• the liver weight/body weight ratio of young mice is significantly higher than controls
• after 4 months of age when large tumor masses are present in the liver, this ratio becomes much larger
• in mice that survive to 12 months of age, liver weight represents nearly 20% of body weight due to invasion of liver tumors into the abdominal cavity
• focal coagulative necrosis of hepatocyte groups with granulocytic reaction is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

tumorigenesis
• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence
• malignant neoplastic lesions appear between the 3 and 4 months of age, with 100% of males and 30% of females having carcinomas by 8 months of age
• the average tumor size for male mice is 1.9 x 1.9 cm and for female mice (0.6 x 1.1 cm)
• most malignant lesions display a trabecular histological pattern but solid or pseudoglandular types are also detectable
• these malignant lesions vary from well differentiated to poorly differentiated with the latter associated with intense mitotic activity, proliferation of neocapillaries, and large areas of hemorrhagic necrosis
• in late stage lesions, small ductular-like cells are found in conjunction with inflammatory cells or scattered among tumor cells and are frequently organized into a duct-like pattern
• dysplastic and neoplastic hepatocytes show the ability to penetrate vascular endothelium and accumulate in the centrilobular veins

cellular
• apoptosis of large dysplastic hepatocytes is sometimes observed as part of larger dysplastic morphology changes in the liver of 2 month old mice

Mouse Models of Human Disease
OMIM IDRef(s)
Hepatocellular Carcinoma 114550 J:34434


Mouse Genome Informatics