Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits

Olga Peñagarikano, Brett S. Abrahams, Edward I. Herman, Kellen D. Winden, Amos Gdalyahu, Hongmei Dong, Lisa I. Sonnenblick, Robin Gruver, Joel Almajano, Anatol Bragin, Peyman Golshani, Joshua T. Trachtenberg, Elior Peles, Daniel H. Geschwind

Research output: Contribution to journalArticle

449 Citations (Scopus)

Abstract

Although many genes predisposing to autism spectrum disorders (ASD) have been identified, the biological mechanism(s) remain unclear. Mouse models based on human disease-causing mutations provide the potential for understanding gene function and novel treatment development. Here, we characterize a mouse knockout of the Cntnap2 gene, which is strongly associated with ASD and allied neurodevelopmental disorders. Cntnap2 -/- mice show deficits in the three core ASD behavioral domains, as well as hyperactivity and epileptic seizures, as have been reported in humans with CNTNAP2 mutations. Neuropathological and physiological analyses of these mice before the onset of seizures reveal neuronal migration abnormalities, reduced number of interneurons, and abnormal neuronal network activity. In addition, treatment with the FDA-approved drug risperidone ameliorates the targeted repetitive behaviors in the mutant mice. These data demonstrate a functional role for CNTNAP2 in brain development and provide a new tool for mechanistic and therapeutic research in ASD. PaperFlick:

Original languageEnglish (US)
Pages (from-to)235-246
Number of pages12
JournalCell
Volume147
Issue number1
DOIs
StatePublished - Sep 30 2011
Externally publishedYes

Fingerprint

Autistic Disorder
Epilepsy
Genes
Risperidone
Therapeutic Human Experimentation
Gene Knockout Techniques
Mutation
Brain
Interneurons
Knockout Mice
Seizures
Pharmaceutical Preparations
Autism Spectrum Disorder

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Peñagarikano, O., Abrahams, B. S., Herman, E. I., Winden, K. D., Gdalyahu, A., Dong, H., ... Geschwind, D. H. (2011). Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell, 147(1), 235-246. https://doi.org/10.1016/j.cell.2011.08.040

Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. / Peñagarikano, Olga; Abrahams, Brett S.; Herman, Edward I.; Winden, Kellen D.; Gdalyahu, Amos; Dong, Hongmei; Sonnenblick, Lisa I.; Gruver, Robin; Almajano, Joel; Bragin, Anatol; Golshani, Peyman; Trachtenberg, Joshua T.; Peles, Elior; Geschwind, Daniel H.

In: Cell, Vol. 147, No. 1, 30.09.2011, p. 235-246.

Research output: Contribution to journalArticle

Peñagarikano, O, Abrahams, BS, Herman, EI, Winden, KD, Gdalyahu, A, Dong, H, Sonnenblick, LI, Gruver, R, Almajano, J, Bragin, A, Golshani, P, Trachtenberg, JT, Peles, E & Geschwind, DH 2011, 'Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits', Cell, vol. 147, no. 1, pp. 235-246. https://doi.org/10.1016/j.cell.2011.08.040
Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H et al. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell. 2011 Sep 30;147(1):235-246. https://doi.org/10.1016/j.cell.2011.08.040
Peñagarikano, Olga ; Abrahams, Brett S. ; Herman, Edward I. ; Winden, Kellen D. ; Gdalyahu, Amos ; Dong, Hongmei ; Sonnenblick, Lisa I. ; Gruver, Robin ; Almajano, Joel ; Bragin, Anatol ; Golshani, Peyman ; Trachtenberg, Joshua T. ; Peles, Elior ; Geschwind, Daniel H. / Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. In: Cell. 2011 ; Vol. 147, No. 1. pp. 235-246.
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