MALE-MICE DEFECTIVE IN THE DNA MISMATCH REPAIR GENE PMS2 EXHIBIT ABNORMAL CHROMOSOME SYNAPSIS IN MEIOSIS

Using gene targeting in embryonic stem cells, we have derived mice wit h a null mutation in a DNA mismatch repair gene homolog, PMS2. We obse rved microsatellite instability in the male germline, in tail, and in tumor DNA of PMS2-deficient animals. We therefore conclude that PMS2 i s involved in DNA mismatch repair in a variety of tissues. PMS2-defici ent animals appear prone to sarcomas and lymphomas, PMS2-deficient mal es are infertile, producing only abnormal spermatozoa. Analysis of axi al element and synaptonemal complex formation during prophase of meios is I indicates abnormalities in chromosome synapsis. These observation s suggest links among mismatch repair, genetic recombination, and chro mosome synapsis in meiosis.