FRAMESHIFT MUTATIONS AT 2 HOTSPOTS IN VASOPRESSIN TRANSCRIPTS IN POSTMITOTIC NEURONS

Mutations in DNA underlie carcinogenesis, inherited pathology, and agi ng and are generally thought to be introduced during meiosis and mitos is. Here we report that in post-mitotic neurons specific frameshift mu tations occur at high frequency. These mutations were identified in va sopressin transcripts in magnocellular neurons of the homozygous Bratt leboro rat and predominantly consist of a GA deletion in GAGAG motifs. Immunocytochemistry provides evidence for similar events in wild-type rats. However, the diseased state of the Brattleboro rat, resulting i n a permanent activation of vasopressin neurons, enhanced the mutation al rate. These data reveal hitherto unrecognized somatic mutations in nondividing neurons.