DNA MISMATCH REPAIR-DEFICIENT MICE IN CANCER-RESEARCH

Biochemical and genetic approaches have been used to demonstrate that basic elements of a DNA mismatch repair (MMR) pathway are conserved be tween bacteria yeast and mammals. Recently, mutations in the human MMR genes MSH2, MLH1, PMS1 and PMS2 have been implicated in a common form of hereditary colon cancer and in sporadic tumors of various tissues. In order to better understand the consequences of MMR deficiency in m ammalian organisms, mice deficient for the Pms2, Mlh1 and Msh2 MMR gen e homologues have been generated. MMR deficient mice display a general increase in spontaneous mutation rate and develop tumors during the f irst year of life. Additionally, loss of MMR appears to accelerate tum origenesis in an Ape deficient background.