FMR1 KNOCKOUT MICE - A MODEL TO STUDY FRAGILE-X MENTAL-RETARDATION

Male patients with fragile X syndrome lack FMR1 protein due to silenci ng of the FMR1 gene by amplification of a CGG repeat and subsequent me thylation of the promoter region. The absence of FMR1 protein leads to mental retardation, aberrant behavior, and macroorchidism. Hardly any thing is known about the physiological function of FMR1 and the pathol ogical mechanisms leading to these symptoms. Therefore, we designed a knockout model for the fragile X syndrome in mice. The knockout mice l ack normal Fmr1 protein and show macroorchidism, learning deficits, an d hyperactivity. Consequently, this knockout mouse may serve as a valu able tool in the elucidation of the physiological role of FMR1 and the mechanisms involved in macroorchidism, abnormal behavior, and mental retardation.