Original Research Article | Published:

Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice

Molecular Psychiatry volume 9, pages 417425 (2004) | Download Citation

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Abstract

Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

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Acknowledgements

These studies were supported by FRAXA Research Foundation grants to PWF and AJS, and to EMD and EMO, and by support from the Virginia Friedhofer Charitable Trust to EMO. We thank Sheena Josselyn and Anna Matynia for comments on earlier versions of this manuscript.

Author information

Author notes

    • P W Frankland

    Current address: Integrative Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada M5G 1X8

Affiliations

  1. Department of Neurobiology, UCLA, Los Angeles, CA 90095, USA

    • P W Frankland
    • , Y Wang
    • , T Shimizu
    •  & A J Silva
  2. Department of Psychiatry, UCLA, Los Angeles, CA 90095, USA

    • P W Frankland
    • , Y Wang
    • , B Rosner
    • , T Shimizu
    • , E M Dykens
    • , E M Ornitz
    •  & A J Silva
  3. Department of Psychology, UCLA, Los Angeles, CA 90095, USA

    • P W Frankland
    • , Y Wang
    • , T Shimizu
    • , B W Balleine
    •  & A J Silva
  4. Brain Research Institute, UCLA, Los Angeles, CA 90095, USA

    • B W Balleine
    • , E M Ornitz
    •  & A J Silva
  5. Mental Retardation Research Center, UCLA, Los Angeles, CA 90095, USA

    • B Rosner
    • , E M Dykens
    •  & A J Silva

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Correspondence to E M Ornitz or A J Silva.

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DOI

https://doi.org/10.1038/sj.mp.4001432

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