Phenotypes Associated with This Genotype

Genotype
MGI:3820248

• Allelic Composition: Gtf2ird1^{Tg(Alb1-Myc)166.8Sst}/Gtf2ird1⁺; Tg(MtTGFA)42Lmb/0
• Genetic Background: involves: C57BL/6 * CBA * CD-1

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

liver/biliary system

increased hepatocyte apoptosis ( J:34434 )

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

increased liver weight ( J:34434 )

• 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

abnormal hepatocyte morphology ( J:34434 )

• most mice by 2 months of age have extensive dysplastic changes in the liver ranging from moderate cellular pleomorphism and hypertrophy to more advanced polymorphisms 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

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

multifocal hepatic necrosis ( J:34434 )

• 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

increased hepatocellular carcinoma incidence ( J:34434 )

• 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

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

neoplasm

increased hepatocellular carcinoma incidence ( J:34434 )

• 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

increased liver adenoma incidence ( J:34434 )

• along with the development of hepatocellular carcinoma, non-malignant tumors also develop with a similar incidence

cellular

increased hepatocyte karyomegaly ( J:34434 )

• by 2 months of age

increased hepatocyte apoptosis ( J:34434 )

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

growth/size/body

increased liver weight ( J:34434 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:34434