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Research Article

Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene

Weiguo Shu, Julie Y. Cho, Yuhui Jiang, Minhua Zhang, Donald Weisz, Gregory A. Elder, James Schmeidler, Rita De Gasperi, Miguel A. Gama Sosa, Donald Rabidou, Anthony C. Santucci, Daniel Perl, Edward Morrisey, and Joseph D. Buxbaum
  1. aMolecular Cardiology Research Center, Department of Medicine, University of Pennsylvania Medical Center, 956 Biomedical Research Building II/III, Philadelphia, PA 19104; cLaboratory of Molecular Neuropsychiatry and Departments of dPsychiatry, eNeuroscience, fNeurosurgery, gNeurology, hOtalaryngology, kPathology, mGeriatrics and Adult Development, and iBiomathematical Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029; and jDepartment of Psychology, Manhattanville College, 2900 Purchase Street, Purchase, NY 10577

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PNAS July 5, 2005 102 (27) 9643-9648; https://doi.org/10.1073/pnas.0503739102
Weiguo Shu
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Julie Y. Cho
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Yuhui Jiang
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Minhua Zhang
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Donald Weisz
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Gregory A. Elder
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James Schmeidler
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Rita De Gasperi
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Miguel A. Gama Sosa
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Donald Rabidou
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Anthony C. Santucci
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Daniel Perl
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Edward Morrisey
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Joseph D. Buxbaum
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  1. Communicated by Peter Palese, Mount Sinai School of Medicine, New York, NY, May 5, 2005 (received for review October 13, 2004)

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Abstract

Neurobiology of speech and language has previously been studied in the KE family, in which half of the members have severe impairment in both speech and language. The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies implicating 7q31 in autism, where language impairment is a component of the disorder, and in specific language impairment, FOXP2 has also been considered as a potential susceptibility locus for the language deficits in autism and/or specific language impairment. In this study, we characterized mice with a disruption in the murine Foxp2 gene. Disruption of both copies of the Foxp2 gene caused severe motor impairment, premature death, and an absence of ultrasonic vocalizations that are elicited when pups are removed from their mothers. Disruption of a single copy of the gene led to modest developmental delay but a significant alteration in ultrasonic vocalization in response to such separation. Learning and memory appear normal in the heterozygous animals. Cerebellar abnormalities were observed in mice with disruptions in Foxp2, with Purkinje cells particularly affected. Our findings support a role for Foxp2 in cerebellar development and in a developmental process that subsumes social communication functions in diverse organisms.

  • autism
  • cerebellum
  • communication
  • language
  • speech

Footnotes

  • ↵ n To whom correspondence should be addressed. E-mail: joseph.buxbaum{at}mssm.edu.

  • ↵ b W.S. and J.Y.C. contributed equally to this work.

  • ↵ l E.M. and J.D.B. contributed equally to this work.

  • Author contributions: W.S., J.Y.C., Y.J., M.Z., D.W., G.A.E., J.S., R.D.G., M.A.G.S., D.R., A.C.S., D.P., E.M., and J.D.B. designed research; W.S., J.Y.C., Y.J., M.Z., D.W., G.A.E., R.D.G., M.A.G.S., D.R., A.C.S., D.P., E.M., and J.D.B. performed research; D.W. and G.A.E. contributed new reagents/analytic tools; W.S., J.Y.C., Y.J., M.Z., D.W., G.A.E., J.S., R.D.G., M.A.G.S., A.C.S., D.P. E.M., and J.D.B. analyzed data; and W.S., J.Y.C., M.Z., D.W., G.A.E., J.S., A.C.S., E.M., and J.D.B. wrote the paper.

  • Abbreviation: EGL, external granular layer.

  • Freely available online through the PNAS open access option.

  • Copyright © 2005, The National Academy of Sciences
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Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene
Weiguo Shu, Julie Y. Cho, Yuhui Jiang, Minhua Zhang, Donald Weisz, Gregory A. Elder, James Schmeidler, Rita De Gasperi, Miguel A. Gama Sosa, Donald Rabidou, Anthony C. Santucci, Daniel Perl, Edward Morrisey, Joseph D. Buxbaum
Proceedings of the National Academy of Sciences Jul 2005, 102 (27) 9643-9648; DOI: 10.1073/pnas.0503739102

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Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene
Weiguo Shu, Julie Y. Cho, Yuhui Jiang, Minhua Zhang, Donald Weisz, Gregory A. Elder, James Schmeidler, Rita De Gasperi, Miguel A. Gama Sosa, Donald Rabidou, Anthony C. Santucci, Daniel Perl, Edward Morrisey, Joseph D. Buxbaum
Proceedings of the National Academy of Sciences Jul 2005, 102 (27) 9643-9648; DOI: 10.1073/pnas.0503739102
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