Reversal of sensorimotor gating abnormalities in Fmr1 knockout mice carrying a human Fmr1 transgene

Behav Neurosci. 2008 Dec;122(6):1371-7. doi: 10.1037/a0013047.

Abstract

Fragile X syndrome is caused by a CGG trinucleotide repeat expansion of the FMR1 gene. Individuals with fragile X display several behavioral abnormalities including hyperactivity, social anxiety, autistic-like features, impaired cognitive processing, and impaired sensorimotor gating. The Fmr1KO 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 Fmr1KO mice with a yeast artificial chromosome containing the human FMR1 gene have corrected or overcorrected abnormal behaviors including hyperactivity and altered social interactions. Here the authors present results from a study examining abnormal sensorimotor gating in Fmr1KO mice. Consistent with previous findings, Fmr1KO mice have increased prepulse inhibition. The KO mice with the yeast artificial chromosome containing the human FMR1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods
  • Animals
  • Behavior, Animal
  • Fragile X Mental Retardation Protein / genetics*
  • Genotype
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition / genetics*
  • Neural Inhibition / physiology
  • Psychophysics
  • Reaction Time
  • Sensory Gating / genetics*

Substances

  • FMR1 protein, human
  • Fmr1 protein, mouse
  • Fragile X Mental Retardation Protein