Reference SummaryShoemaker AR, Oncogene 2000 May 25;19(23):2774-9

Title

 Mlh1 deficiency enhances several phenotypes of Apc(Min)/+ mice.

Authors

 Shoemaker AR; Haigis KM; Baker SM; Dudley S; Liskay RM; Dove WF

Journal

 Oncogene

Volume

 19

Issue

 23

Year

 2000

Pages

 2774-9

Abstract

 Defects in APC and DNA mismatch repair genes are associated with a strong predisposition to colon cancer in humans, and numerous mouse strains with mutations in these genes have been generated. In this report we describe the phenotype of Min/+ Mlh1-/- mice. We find that these doubly mutant mice develop more than three times the number of intestinal adenomas compared to Min/+ Mlh1+/+ or +/- mice but that these tumors do not show advanced progression in terms of tumor size or histological appearance. Full length Apc protein was not detected in the tumor cells from Min/+ Mlh1-/- mice. Molecular analyses indicated that in many tumors from Min/+ Mlh1-/- mice, Apc was inactivated by intragenic mutation. Mlh1 deficiency in Min/+ mice also led to an increase in cystic intestinal crypt multiplicity as well as enhancing desmoid tumorigenesis and epidermoid cyst development. Thus, Mlh1 deficiency influences the somatic events involved in the development of most of the phenotypes associated with the Min mutation. Oncogene (2000).

Links

 J:62824 – MGI References
10851078 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;129S7-ApcMin/+ In this study the genetic background of the mice was approximately 94% C57BL/6J and 6% 129S7/SvEvBrd (N4 onto C57BL/6J).
B6;129S7-ApcMin/+ Mlh1tm1Lisk In this study the genetic background of the mice was approximately 94% C57BL/6J and 6% 129S7/SvEvBrd (N4 onto C57BL/6J).
B6;129S7-ApcMin/+ Mlh1tm1Lisk/+ In this study the genetic background of the mice was approximately 94% C57BL/6J and 6% 129S7/SvEvBrd (N4 onto C57BL/6J).

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6;129S7-ApcMin/+ Mlh1tm1Lisk Connective tissue - Fibroblast desmoid Connective tissue - Fibroblast

36
B6;129S7-ApcMin/+ Mlh1tm1Lisk/+ Connective tissue - Fibroblast desmoid Connective tissue - Fibroblast

0
B6;129S7-ApcMin/+ Connective tissue - Fibroblast desmoid Connective tissue - Fibroblast

4.5
B6;129S7-ApcMin/+ Mlh1tm1Lisk Intestine adenoma Intestine

very high
B6;129S7-ApcMin/+ Mlh1tm1Lisk/+ Intestine adenoma Intestine

very high
B6;129S7-ApcMin/+ Intestine adenoma Intestine

very high
C57BL/6J-ApcMin/+ Intestine adenoma Intestine

observed
B6;129S7-ApcMin/+ Mlh1tm1Lisk Intestine cyst Intestine

very high
B6;129S7-ApcMin/+ Mlh1tm1Lisk/+ Intestine cyst Intestine

very high
B6;129S7-ApcMin/+ Intestine cyst Intestine

very high
B6;129S7-ApcMin/+ Mlh1tm1Lisk Skin - Dermis cyst - epidermoid Skin - Dermis

50
B6;129S7-ApcMin/+ Mlh1tm1Lisk/+ Skin - Dermis cyst - epidermoid Skin - Dermis

0
B6;129S7-ApcMin/+ Skin - Dermis cyst - epidermoid Skin - Dermis

0