Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice

• Published in: Cancer research (Chicago, Ill.) Vol. 56; no. 16; pp. 3842 - 3849
• Main Authors: REITMAIR, A. H, REDSTON, M, JIAN CHUN CAI, CHUANG, T. C. Y, BJERKNES, M, CHENG, H, HAY, K, GALLINGER, S, BAPAT, B, MAK, T. W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.1996
• Subjects: Adenomatous Polyposis Coli Protein; Animals; Base Sequence; Biological and medical sciences; Cytoskeletal Proteins - analysis; DNA Repair; DNA-Binding Proteins - analysis; DNA-Binding Proteins - genetics; Female; Fungal Proteins; Gastroenterology. Liver. Pancreas. Abdomen; Intestinal Neoplasms - etiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Microsatellite Repeats; Molecular Sequence Data; MutS Homolog 2 Protein; Skin Neoplasms - etiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Animal model; Skin disease; Carcinoma; Pathogenesis; Deficiency; Rodentia; Malignant tumor; Genetic disease; Vertebrata; Mammalia; Mouse; Microsatellite DNA; DNA; Rectum; Digestive diseases; Intestinal disease; Instability; Skin; Colon; Repair
• ISSN: 0008-5472; 1538-7445

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.