Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice.
Analysis of two human familial cancer syndromes, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis, indicates that mutations in either one of four DNA mismatch repair gene homologues or the adenomatous polyposis coli (APC) gene, respectively, are important for the development of colorectal cancer. To further investigate the role of DNA mismatch repair in intestinal tumorigenesis, we generated mice with mutations in both Apc and the DNA mismatch repair gene, Pms2. Whereas Pms2-deficient mice do not develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of Apc, develop approximately three times the number of small intestinal adenomas and four times the number of colon adenomas relative to Min and Pms2+/-;Min mice. Although Pms2 deficiency clearly increases adenoma formation in the Min background, histological analysis indicated no clear evidence for progression to carcinoma.
Baker
S M
SM
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Harris
A C
AC
Tsao
J L
JL
Flath
T J
TJ
Bronner
C E
CE
Gordon
M
M
Shibata
D
D
Liskay
R M
RM
D000236:Adenoma / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein; D000251:Adenosine Triphosphatases; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D007417:Intestinal Polyps / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats / Q000235:genetics; D000070976:Mismatch Repair Endonuclease PMS2; D009374:Neoplasms, Experimental; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000502:physiology*
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D000251:Adenosine Triphosphatases; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes