Reversal of Sensorimotor Gating Abnormalities in Fmr1 Knockout Mice Carrying a Human FMR1 Transgene.

Fragile X syndrome is caused by a CGG trinucleotide repeat expansion of the FMRI gene. Individuals with fragile X display several behavioral abnormalities including hyperactivity, social anxiety, autistic-like features, impaired cognitive processing, and impaired sensorimotor gating. The FmrIKO mouse model of fragile X exhibits several related behavioral phenotypes such as increased activity and altered social interactions. Individuals with fragile X also have impaired sensorimotor gating as measured using the prepulse inhibition of startle response. The authors have recently shown that FmrlKO mice with a yeast artificial chromosome containing the human FMR I gene have connected or overeorrected abnormal behaviors including hyperactivity and altered social interactions. Here the authors present results from a study examining abnormal sensorimotor gating in FmrlKO mice. Consistent with previous findings, FmrlKO mice have increased prepulse inhibition. The KO mice with the yeast artificial chromosome containing the human FMRJ gene had levels of prepulse inhibition comparable to WT mice, indicating not only a correction of this phenotype, but also clearly demonstrating that in mice levels of the fragile X mental retardation protein regulate sensorimotor gating. [ABSTRACT FROM AUTHOR]