Reference SummaryLaird PW, Cell 1995 Apr 21;81(2):197-205

Title

 Suppression of intestinal neoplasia by DNA hypomethylation.

Authors

 Laird PW; Jackson-Grusby L; Fazeli A; Dickinson SL; Jung WE; Li E; Weinberg RA; Jaenisch R

Journal

 Cell

Volume

 81

Issue

 2

Year

 1995

Pages

 197-205

Abstract

 We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on ApcMin-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-aza-deoxycytidine, reduced the average number of intestinal adenomas from 113 in the control mice to only 2 polyps in the treated heterozygotes. Hence, DNA methyltransferase activity contributes substantially to tumor development in this mouse model of intestinal neoplasia. Our results argue against an oncogenic effect of DNA hypomethylation. Moreover, they are consistent with a role for DNA methyltransferase in the generation of the C to T transitions seen at high frequency in human colorectal tumors.

Links

 J:25691 – MGI References
7537636 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;129-ApcMin/+ Mice were generated by mating C57BL/6-ApcMin/+ males to 129/Sv females.
C57BL/6-ApcMin/+ Mice were generated by mating C57BL/6J-ApcMin/+J males purchased from The Jackson Laboratory to C57BL/6 females.
[not specified] Mice were generated by mating ApcMin/+ males purchased from The Jackson Laboratory with Dnmttm1Enl females.
Treatment with 5-aza-2'-deoxycytidine had no significant effect on body weight.
[not specified]-ApcMin/+ Mice were generated by mating ApcMin/+ males purchased from The Jackson Laboratory with Dnmttm1Enl females.
Treatment with 5-aza-2'-deoxycytidine had no significant effect on body weight.
[not specified]-ApcMin/+ Dnmt1tm1Enl/+ Mice were generated by mating ApcMin/+ males purchased from The Jackson Laboratory with Dnmttm1Enl females.
Treatment with 5-aza-2'-deoxycytidine had no significant effect on body weight.
[not specified]-Dnmt1tm1Enl/+ Mice were generated by mating ApcMin/+ males purchased from The Jackson Laboratory with Dnmttm1Enl females.
Treatment with 5-aza-2'-deoxycytidine had no significant effect on body weight.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-ApcMin/+ Intestine adenoma
  • 5-aza-2'-deoxycytidine (5-aza-dC) (decitabine) (DAC)
 Intestine

observed
[not specified]-ApcMin/+ Intestine adenoma Intestine

observed
[not specified]-ApcMin/+ Dnmt1tm1Enl/+ Intestine adenoma
  • 5-aza-2'-deoxycytidine (5-aza-dC) (decitabine) (DAC)
 Intestine

observed
[not specified]-ApcMin/+ Dnmt1tm1Enl/+ Intestine adenoma Intestine

observed
[not specified]-Dnmt1tm1Enl/+ Intestine adenoma
  • 5-aza-2'-deoxycytidine (5-aza-dC) (decitabine) (DAC)
 Intestine

0
[not specified]-Dnmt1tm1Enl/+ Intestine adenoma Intestine

0
[not specified] Intestine adenoma
  • 5-aza-2'-deoxycytidine (5-aza-dC) (decitabine) (DAC)
 Intestine

0
[not specified] Intestine adenoma Intestine

0
C57BL/6-ApcMin/+ Intestine adenoma Intestine

observed
C57BL/6-ApcMin/+ Intestine adenoma
  • 5-aza-2'-deoxycytidine (5-aza-dC) (decitabine) (DAC)
 Intestine

observed
B6;129-ApcMin/+ Intestine adenoma
  • 5-aza-2'-deoxycytidine (5-aza-dC) (decitabine) (DAC)
 Intestine

observed
B6;129-ApcMin/+ Intestine adenoma Intestine

observed