Reference SummaryTang B, Nat Med 1998 Jul;4(7):802-7

Title

 Transforming growth factor-beta1 is a new form of tumor suppressor with true haploid insufficiency.

Authors

 Tang B; Bottinger EP; Jakowlew SB; Bagnall KM; Mariano J; Anver MR; Letterio JJ; Wakefield LM

Journal

 Nat Med

Volume

 4

Issue

 7

Year

 1998

Pages

 802-7

Abstract

 Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-betas themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta1 gene express only 10-30% of wild-type TGF-beta1 protein levels. Although grossly normal, these mice have a subtly altered proliferative phenotype, with increased cell turnover in the liver and lung. Treatment of these mice with chemical carcinogens resulted in enhanced tumorigenesis when compared with wild-type littermates. However, tumors in the heterozygous mice did not lose the remaining wild-type TGF-beta1 allele, indicating that the TGF-beta1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis.

Links

 J:78174 – MGI References
9662371 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129S6-Tgfb1tm1N/+ Mice carrying the targeted mutant allele on a mixed genetic background (C57BL/6J and "129/Sv" [substrain not specified, but it at least included 129S6/SvEvTac]) were backcrossed 6 times onto C57BL/6NCr.
Protein levels of Tgfb1 in normal tissues is 11-30% reduced compared to that observed in wild type mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular adenoma Liver

0
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular adenoma
  • diethylnitrosamine (DEN)
 Liver

observed - 20
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular adenoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Liver

0 - 29
C57BL/6NCr Liver hepatocellular adenoma Liver

0
C57BL/6NCr Liver hepatocellular adenoma
  • diethylnitrosamine (DEN)
 Liver

0
C57BL/6NCr Liver hepatocellular adenoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Liver

0 - 9.1
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular carcinoma Liver

0
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular carcinoma
  • diethylnitrosamine (DEN)
 Liver

0
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular carcinoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Liver

0 - 25
C57BL/6NCr Liver hepatocellular carcinoma Liver

0
C57BL/6NCr Liver hepatocellular carcinoma
  • diethylnitrosamine (DEN)
 Liver

0 - 9.1
C57BL/6NCr Liver hepatocellular carcinoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Liver

0
B6.129S6-Tgfb1tm1N/+ Liver hepatocellular tumor
  • diethylnitrosamine (DEN)
 Liver

44
C57BL/6NCr Liver hepatocellular tumor
  • diethylnitrosamine (DEN)
 Liver

36
B6.129S6-Tgfb1tm1N/+ Liver hyperplasia Liver

0
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus adenoma Lung - Alveolus

5.3
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus adenoma
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0 - observed
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus adenoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0
C57BL/6NCr Lung - Alveolus adenoma Lung - Alveolus

0
C57BL/6NCr Lung - Alveolus adenoma
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0
C57BL/6NCr Lung - Alveolus adenoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0 - 9.1
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus carcinoma Lung - Alveolus

0
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus carcinoma
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0 - 29
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus carcinoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0 - 4.8
C57BL/6NCr Lung - Alveolus carcinoma Lung - Alveolus

0
C57BL/6NCr Lung - Alveolus carcinoma
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0
C57BL/6NCr Lung - Alveolus carcinoma
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Lung - Alveolus

0
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus tumor
  • diethylnitrosamine (DEN)
 Lung - Alveolus

79
B6.129S6-Tgfb1tm1N/+ Lung - Alveolus tumor
  • phenobarbital (PB)
  • diethylnitrosamine (DEN)
 Lung - Alveolus

52
C57BL/6NCr Lung - Alveolus tumor
  • diethylnitrosamine (DEN)
 Lung - Alveolus

60
B6.129S6-Tgfb1tm1N/+ Lung hyperplasia Lung

0