Tg(tetO-MET)23Rwng Transgene Detail MGI Mouse (MGI:3810467)

Tg(tetO-MET)23Rwng
Transgene Detail

Nomenclature

Symbol:	Tg(tetO-MET)23Rwng
Name:	transgene insertion 23, Rong Wang
MGI ID:	MGI:3810467
Synonyms:	TRE-hMET, TRE-MET
Transgene:	Tg(tetO-MET)23Rwng Location: unknown

Transgene
origin

Strain of Origin:

FVB/N

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The TRE-MET transgene was designed with the human MET (met proto-oncogene (hepatocyte growth factor receptor)) coding sequence, under the control of heptamerized tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) sequences and a cytomegalovirus (hCMV) minimal promoter with a beta-globin poly A signal. Founder line 23 was subsequently established. (J:69731)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 1 strain available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

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Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1
growth/size		√
cachexia		√
		tg1
life span/aging		√
premature death		√
		tg1
liver/biliary system		√
abnormal hepatocyte morphology		√
enlarged liver		√
focal hepatic necrosis		√
hepatic steatosis		√
jaundice		√
		tg1
tumorigenesis		√
hepatocellular carcinoma		√

		tg1
Disease Models		√
Hepatocellular Carcinoma		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(tetO-MET)23Rwng/0
Tg(tTALap)5Bjd/0

involves: FVB/N * NMRI

life span/agingpremature death (J:69731)

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/sizecachexia (J:69731)

animals dying without evidence of tumors are usually cachexic

liver/biliary systemabnormal hepatocyte morphology (J:69731)

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

enlarged liver (J:69731)

pups are born with enlarged and fatty livers

focal hepatic necrosis (J:69731)

fully developed tumors often display areas of necrosis

hepatic steatosis (J:69731)

pups are born with enlarged and fatty livers

jaundice (J:69731)

animals dying without evidence of tumors display jaundice

tumorigenesishepatocellular carcinoma (J:69731)

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

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Hepatocellular Carcinoma		J:69731

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models involving transgenes or other mutation types.¹
Hepatocellular Carcinoma OMIM ID: 114550		tg1	Tg(tetO-MET)23Rwng/0 Tg(tTALap)5Bjd/0	involves: FVB/N * NMRI	J:69731

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

References

Original:	J:69731 Wang R et al., "Activation of the met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice." J Cell Biol 2001 May 28;153(5):1023-34
All:	2 reference(s)

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