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Phenotypes Associated with This Genotype
Genotype
MGI:3810811
Allelic
Composition
Tg(tetO-MET)23Rwng/0
Tg(Cebpb-tTA)5Bjd/0
Genetic
Background
involves: FVB/N * NMRI
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Cebpb-tTA)5Bjd mutation (3 available)
Tg(tetO-MET)23Rwng mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice from 2 lines (1 and 2) of double transgenic founders die within 2 months postpartum; early mortality can be prevented by repression of MET expression with doxycycline administration to mating parents, and then to pups until 4 weeks of age
• with this doxycycline treatment, animals appear normal until 10 months of age, then mice start dying
• mice from 2 other lines (3 and 4) of double transgenic parents are healthy at birth, then begin to die at 4 months of age

growth/size/body
• animals dying without evidence of tumors are usually cachexic
• pups are born with enlarged and fatty livers

liver/biliary system
• fully developed tumors often display areas of necrosis
• pups are born with enlarged and fatty livers
• hepatocytes in foci of hyperplasia develop foamy cytoplasm containing fat deposits
• with progression of hyperplastic foci toward malignancy, cytologic changes are observed such as cellular and nuclear enlargement with disorganization of cell plate and lobular structures; malignant foci enlarge and develop trabeculae lined with endothelial cells, often separated from each other by blood-filled spaces
• pups are born with enlarged and fatty livers
• 85% of animals dying after 10 months after receiving DOX till 4 weeks of age show hepatocellular carcinoma (HCC); incidence by 1 year is >60% in lines 1 and 2
• for lines 3 and 4, 85% of deaths are accompanied by HCC, which appears as an abdominal mass at 6 months of age or later; incidence by 1 year is 60%
• by 60 weeks of age, many small foci of hyperplasia are detected, often around central hepatic lobule and become more numerous, larger, and uniformly distributed by 4 months of age
• zones of progression to malignancy are observed within hyperplasias by 6 months, with cells in the zones showing poor organization and less differentiation than normal livers
• majority of moribund mice treated with doxycycline regain health tumors nearly regress completely, with liver morphology becoming almost normal by 4 months of treatment
• fully developed tumors often display areas of necrosis
• animals dying without evidence of tumors display jaundice

neoplasm
• 85% of animals dying after 10 months after receiving DOX till 4 weeks of age show hepatocellular carcinoma (HCC); incidence by 1 year is >60% in lines 1 and 2
• for lines 3 and 4, 85% of deaths are accompanied by HCC, which appears as an abdominal mass at 6 months of age or later; incidence by 1 year is 60%
• by 60 weeks of age, many small foci of hyperplasia are detected, often around central hepatic lobule and become more numerous, larger, and uniformly distributed by 4 months of age
• zones of progression to malignancy are observed within hyperplasias by 6 months, with cells in the zones showing poor organization and less differentiation than normal livers
• majority of moribund mice treated with doxycycline regain health tumors nearly regress completely, with liver morphology becoming almost normal by 4 months of treatment
• fully developed tumors often display areas of necrosis

cellular
• fully developed tumors often display areas of necrosis

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
hepatocellular carcinoma DOID:684 OMIM:114550
J:69731


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
03/12/2024
MGI 6.23
The Jackson Laboratory