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

Alex R. Shoemaker, Kevin M. Haigis, Sean M. Baker, Sandy Dudley, Robert (Mike) Liskay, William F. Dove

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2774-2779
Number of pages6
JournalOncogene
Volume19
Issue number23
StatePublished - May 25 2000

Fingerprint

Phenotype
Mutation
Neoplasms
Aggressive Fibromatosis
Epidermal Cyst
DNA Mismatch Repair
Adenoma
Colonic Neoplasms
Genes
Carcinogenesis
Proteins

Keywords

  • Apc
  • Min
  • Mlh1
  • Mutation
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Shoemaker, A. R., Haigis, K. M., Baker, S. M., Dudley, S., Liskay, R. M., & Dove, W. F. (2000). Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice. Oncogene, 19(23), 2774-2779.

Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice. / Shoemaker, Alex R.; Haigis, Kevin M.; Baker, Sean M.; Dudley, Sandy; Liskay, Robert (Mike); Dove, William F.

In: Oncogene, Vol. 19, No. 23, 25.05.2000, p. 2774-2779.

Research output: Contribution to journalArticle

Shoemaker, AR, Haigis, KM, Baker, SM, Dudley, S, Liskay, RM & Dove, WF 2000, 'Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice', Oncogene, vol. 19, no. 23, pp. 2774-2779.
Shoemaker AR, Haigis KM, Baker SM, Dudley S, Liskay RM, Dove WF. Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice. Oncogene. 2000 May 25;19(23):2774-2779.
Shoemaker, Alex R. ; Haigis, Kevin M. ; Baker, Sean M. ; Dudley, Sandy ; Liskay, Robert (Mike) ; Dove, William F. / Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice. In: Oncogene. 2000 ; Vol. 19, No. 23. pp. 2774-2779.
@article{c2526a7ac0f94f06ac0c8968f93e0cf2,
title = "Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice",
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.",
keywords = "Apc, Min, Mlh1, Mutation, Tumor",
author = "Shoemaker, {Alex R.} and Haigis, {Kevin M.} and Baker, {Sean M.} and Sandy Dudley and Liskay, {Robert (Mike)} and Dove, {William F.}",
year = "2000",
month = "5",
day = "25",
language = "English (US)",
volume = "19",
pages = "2774--2779",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "23",

}

TY - JOUR

T1 - Mlh1 deficiency enhances several phenotypes of Apc(Min/+) mice

AU - Shoemaker, Alex R.

AU - Haigis, Kevin M.

AU - Baker, Sean M.

AU - Dudley, Sandy

AU - Liskay, Robert (Mike)

AU - Dove, William F.

PY - 2000/5/25

Y1 - 2000/5/25

N2 - 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.

AB - 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.

KW - Apc

KW - Min

KW - Mlh1

KW - Mutation

KW - Tumor

UR - http://www.scopus.com/inward/record.url?scp=0034713460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034713460&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 2774

EP - 2779

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 23

ER -