Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice.
Hereditary nonpolyposis colorectal cancer is associated with defects in DNA mismatch repair. Here, we characterize tumor susceptibility of the recently described Msh2-deficient mouse model. Within the first year of observation, all homozygous mice succumbed to disease, with lymphomas observed in at least 80% of the cases. The majority (70%) of animals 6 months or older developed intestinal neoplasms associated with APC inactivation. Microsatellite instability was more common in carcinomas than in adenomas, but uncommon in normal tissues. Some animals (7%) developed a variety of skin neoplasms analogous to the Muir-Torre syndrome. Msh2-/- mice implicate a direct role for mismatch repair in several neoplasms with striking phenotypic similarities to humans.
Reitmair
A H
AH
Department of Medical Biophysics, Ontario Cancer Institute/Amgen Institute, University of Toronto, Ontario, Canada.
Redston
M
M
Cai
J C
JC
Chuang
T C
TC
Bjerknes
M
M
Cheng
H
H
Hay
K
K
Gallinger
S
S
Bapat
B
B
Mak
T W
TW
D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000032:analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D005656:Fungal Proteins; D007414:Intestinal Neoplasms / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D012878:Skin Neoplasms / Q000209:etiology*
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051718:MutS Homolog 2 Protein