Fragile X mice develop sensory hyperreactivity to auditory stimuli

Neuroscience. 2001;103(4):1043-50. doi: 10.1016/s0306-4522(01)00036-7.


Fragile X syndrome is the most prevalent cause of mental retardation. It is usually caused by the transcriptional inactivation of the FMR-1 gene. Although the cognitive defect is the most recognized symptom of fragile X syndrome, patients also show behavioral problems such as hyperarousal, hyperactivity, autism, aggression, anxiety and increased sensitivity to sensory stimuli. Here we investigated whether fragile X mice (fmr-1 gene knockout mice) exhibit abnormal sensitivity to sensory stimuli. First, hyperreactivity of fragile X mice to auditory stimulus was indicated in the prepulse inhibition paradigm. A moderately intense prepulse tone, that suppresses startle response to a strong auditory stimulus, elicited a significantly stronger effect in fragile X than in control mice. Second, sensory hyperreactivity of fragile X mice was demonstrated by a high seizure susceptibility to auditory stimulation. Selective induction of c-Fos, an early-immediate gene product, indicated that seizures involve auditory brainstem and thalamic nuclei. Audiogenic seizures were not due to a general increase in brain excitability because three different chemical convulsants (kainic acid, bicuculline and pentylenetetrazole) elicited similar effects in fragile X and wild-type mice. These data are consistent with the increased responsiveness of fragile X patients to auditory stimuli. The auditory hypersensitivity suggests an abnormal processing in the auditory system of fragile X mice, which could provide a useful model to study the molecular and cellular changes underlying fragile X syndrome.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Behavior, Animal*
  • Brain Stem / metabolism
  • Convulsants
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / psychology*
  • Genetic Predisposition to Disease
  • Mice
  • Mice, Knockout / genetics
  • Nerve Tissue Proteins / genetics
  • Neural Inhibition
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA-Binding Proteins*
  • Reference Values
  • Reflex, Startle
  • Seizures / chemically induced
  • Seizures / genetics
  • Seizures / metabolism
  • Thalamus / metabolism


  • Convulsants
  • Fmr1 protein, mouse
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein