Reference SummarySchreiber-Agus N, Nature 1998 Jun 4;393(6684):483-7

Title

 Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth.

Authors

 Schreiber-Agus N; Meng Y; Hoang T; Hou H Jr; Chen K; Greenberg R; Cordon-Cardo C; Lee HW; DePinho RA

Journal

 Nature

Volume

 393

Issue

 6684

Year

 1998

Pages

 483-7

Abstract

 Mxi1 belongs to the Mad (Mxi1) family of proteins, which function as potent antagonists of Myc oncoproteins. This antagonism relates partly to their ability to compete with Myc for the protein Max and for consensus DNA binding sites and to recruit transcriptional co-repressors. Mad(Mxi1) proteins have been suggested to be essential in cellular growth control and/or in the induction and maintenance of the differentiated state. Consistent with these roles, mxi1 may be the tumour-suppressor gene that resides at region 24-26 of the long arm of chromosome 10. This region is a cancer hotspot, and mutations here may be involved in several cancers, including prostate adenocarcinoma. Here we show that mice lacking Mxi1 exhibit progressive, multisystem abnormalities. These mice also show increased susceptibility to tumorigenesis either following carcinogen treatment or when also deficient in Ink4a. This cancer-prone phenotype may correlate with the enhanced ability of several mxi1-deficient cell types, including prostatic epithelium, to proliferate. Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner.

Links

 J:48236 – MGI References
9624006 – National Library of Medicine/PubMed

Strain Notes

Strain Note
[not specified] Wildtype controls for targeted mutant mice.
STOCK Cdkn2atm1Rdp These mice were generated using the WW6 ES cell line (75% 129/Sv, 20% C57BL/6, 5% SJL). Chimeric males were mated to C57BL/6 females. Offspring were then intercrossed to generate mice wild type, heterozygous, and homozygous for the mutant allele.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Mxi1tm1Rdp CNS - Brain - Glial cell glioma CNS - Brain - Glial cell

0
[not specified] Leukocyte - Lymphocyte - B-lymphocyte lymphoma Leukocyte - Lymphocyte - B-lymphocyte

0
[not specified]-Mxi1tm1Rdp Leukocyte - Lymphocyte - B-lymphocyte lymphoma Leukocyte - Lymphocyte - B-lymphocyte

observed
[not specified] Leukocyte lymphoma
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Leukocyte

observed
[not specified]-Mxi1tm1Rdp Leukocyte lymphoma
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Leukocyte

observed
[not specified]-Mxi1tm1Rdp Prostate gland hyperplasia Prostate gland

55
[not specified] Prostate gland hyperplasia Prostate gland

25
[not specified] Skin squamous cell carcinoma
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Skin

observed
[not specified]-Mxi1tm1Rdp Skin squamous cell carcinoma
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Skin

observed
[not specified]-Mxi1tm1Rdp Spleen - White pulp hyperplasia Spleen - White pulp

33
[not specified]-Mxi1tm1Rdp (Unspecified organ) tumor
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 (Unspecified organ)

65
[not specified] (Unspecified organ) tumor
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 (Unspecified organ)

25
STOCK Cdkn2atm1Rdp (Unspecified organ) tumor
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 (Unspecified organ)

20
[not specified]-Cdkn2atm1Rdp Mxi1tm1Rdp (Unspecified organ) tumor
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 (Unspecified organ)

56