Phenotypes Associated with This Genotype

Genotype
MGI:5544915

• Allelic Composition: Tg(HBVX*,-Myc)#Skp/Tg(HBVX*,-Myc)#Skp
• Genetic Background: Not Specified

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

growth/size/body

enlarged liver ( J:81098 )

• progressive liver enlargement with a most noticeable increase from 20 weeks

increased liver weight ( J:81098 )

• increase in liver weight, that is most noticeable after 20 weeks of life

liver/biliary system

abnormal liver morphology ( J:81098 )

• liver begins to appear nodular, congested and firm in consistency at 28 weeks of age

liver vascular congestion ( J:81098 )

• liver begins to appear congested at 28 weeks of age

enlarged liver ( J:81098 )

• progressive liver enlargement with a most noticeable increase from 20 weeks

increased liver weight ( J:81098 )

• increase in liver weight, that is most noticeable after 20 weeks of life

decreased liver glycogen level ( J:81098 )

• abundant glycogen is seen in hepatocytes up to 4 weeks of age, which then gradually diminishes and remains periportal in location, unlike in controls which show glycogen at all stages

increased liver iron level ( J:81098 )

• iron is seen in the dysplastic hepatocytes around the central veins but not in tumor cells

abnormal liver lobule morphology ( J:81098 )

• expansion of hepatic lobules with a clustering of large numbers of central veins in a given field with spaced out portal tracts at the periphery from 4 weeks of age onwards

abnormal liver sinusoid morphology ( J:81098 )

• apoptotic bodies are seen scattered in the sinusoids

abnormal hepatocyte morphology ( J:81098 )

• cytological changes in hepatocytes start as early as day 3 and show swelling, an increase in proliferation accompanied by a high rate of apoptosis which declines once tumors form

• from day 7, hepatocytes show progressive nuclear enlargement, vesicular chromatin, prominent, single or multiple nucleoli, nuclear pleomorphism, and typical and atypical mitosis

• by day 14, nuclear enlargement is seen, some with abnormal contours, while cytoplasm contains numerous mitochondria including abnormal forms

• cytoplasm of hepatocytes becomes more basophilic after 4 weeks

• abundant glycogen is seen in hepatocytes up to 4 weeks of age, which then gradually diminishes and remains periportal in location, unlike in controls which show glycogen at all stages

• iron is seen in the dysplastic hepatocytes around the central veins but not in tumor cells

abnormal hepatocyte mitochondrial morphology ( J:202732 )

focal hepatic necrosis ( J:81098 )

• focal necrosis is seen about 8-12 weeks of age

microvesicular hepatic steatosis ( J:81098 )

• mild microvesicular fatty change in the hepatocytes around the central veins at weeks 4-5

• however, cirrhosis is not seen

increased hepatocellular carcinoma incidence ( J:81098 )

• multiple tumor nodules are seen on the surface of the liver between 28 and 32 weeks

• tumor nodules show central necrosis

• between 24-32 weeks of age, multifocal, well-differentiated, hepatocellular carcinoma with a trabecular pattern emerges

• malignant hepatocyte cords show large pleomorphic nuclei with multinucleation and macronucleoli

• by 16-20 weeks, multiple dysplastic foci are incorporated into distinct neoplastic nodules that compress the surrounding liver parenchyma and nodules show compressed reticulin at the periphery

neoplasm

increased hepatocellular carcinoma incidence ( J:81098 )

• multiple tumor nodules are seen on the surface of the liver between 28 and 32 weeks

• tumor nodules show central necrosis

• between 24-32 weeks of age, multifocal, well-differentiated, hepatocellular carcinoma with a trabecular pattern emerges

• malignant hepatocyte cords show large pleomorphic nuclei with multinucleation and macronucleoli

• by 16-20 weeks, multiple dysplastic foci are incorporated into distinct neoplastic nodules that compress the surrounding liver parenchyma and nodules show compressed reticulin at the periphery

cardiovascular system

abnormal liver sinusoid morphology ( J:81098 )

• apoptotic bodies are seen scattered in the sinusoids

liver vascular congestion ( J:81098 )

• liver begins to appear congested at 28 weeks of age

hematopoietic system

abnormal definitive hematopoiesis ( J:81098 )

• livers show an early disappearance of foci of extramedullary hematopoiesis in the portal tracts by day 14 compared to controls which show persistence of extramedullary hematopoiesis by the 4th week

increased macrophage cell number ( J:81098 )

• Kupffer cells appear prominent between 4 and 12 weeks of age

homeostasis/metabolism

decreased liver glycogen level ( J:81098 )

• abundant glycogen is seen in hepatocytes up to 4 weeks of age, which then gradually diminishes and remains periportal in location, unlike in controls which show glycogen at all stages

increased liver iron level ( J:81098 )

• iron is seen in the dysplastic hepatocytes around the central veins but not in tumor cells

immune system

increased macrophage cell number ( J:81098 )

• Kupffer cells appear prominent between 4 and 12 weeks of age

cellular

abnormal cell nucleus morphology ( J:202732 )

• liver shows an increase in the number of nucleolar organizer regions

abnormal hepatocyte mitochondrial morphology ( J:202732 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:81098 , J:202732