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 – Mouse Genome Informatics
10851078 – National Library of Medicine/PubMed

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