Reference SummaryJhappan C, Cell 1990 Jun 15;61(6):1137-46

Title

 TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.

Authors

 Jhappan C; Stahle C; Harkins RN; Fausto N; Smith GH; Merlino GT

Journal

 Cell

Volume

 61

Issue

 6

Year

 1990

Pages

 1137-46

Abstract

 To define the role of TGF alpha in normal tissue function and in pathogenesis, transgenic mice have been generated bearing a fusion gene consisting of the mouse metallothionein 1 promoter and a human TGF alpha cDNA. In these mice, human TGF alpha RNA and protein are abundant in many tissues and TGF alpha is detectable in blood and urine. The effects of TGF alpha overproduction in transgenic mice are pleiotropic and tissue specific. The liver frequently contains multifocal, well-differentiated hepatocellular carcinomas that express enhanced levels of human TGF alpha RNA. The mammary gland exhibits impeded morphogenetic penetration of epithelial duct cells into the stromal fat pad. The pancreas shows progressive interstitial fibrosis and a florid acinoductular metaplasia, during which acinar cells appear to degranulate, dedifferentiate, and assume characteristics of intercalated or centroacinar duct cells. TGF alpha therefore plays an important role in cellular proliferation, organogenesis, and neoplastic transformation.

Links

 J:28452 – MGI References
2350785 – National Library of Medicine/PubMed

Strain Notes

Strain Note
CD-1-Tg(MtTGFA)42Lmb Injection of zinc raised levels of transgene expression in breast, liver, and pancreas.
These mice may be homozygous or hemizygous.
The transgene stably inserted at a single site with two copies per haploid genome.
The transgene was expressed at a high level in many tissues: liver, pancreas, kidney, stomach. It was also expressed at lower levels in bone, breast, brain, colon, lung, skeletal muscle, testis, uterus. Transgene expression in the liver was 5 times higher in females than in males.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1-Tg(MtTGFA)42Lmb Liver adenoma - clear cell Liver

observed
CD-1-Tg(MtTGFA)42Lmb Liver dysplasia
  • (see notes)
 Liver

observed
CD-1-Tg(MtTGFA)42Lmb Liver dysplasia Liver

observed
CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma Liver

observed
CD-1-Tg(MtTGFA)42Lmb Liver hepatocellular carcinoma
  • (see notes)
 Liver

65
CD-1 Liver tumor Liver

0
CD-1-Tg(MtTGFA)42Lmb Pancreas - Duct metaplasia
  • ZnCl2
 Pancreas - Duct

observed