A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

Wolfgang Enard*, Sabine Gehre, Kurt Hammerschmidt, Sabine M. Hölter, Torsten Blass, Mehmet Somel, Martina K. Brückner, Christiane Schreiweis, Christine Winter, Reinhard Sohr, Lore Becker, Victor Wiebe, Birgit Nickel, Thomas Giger, Uwe Müller, Matthias Groszer, Thure Adler, Antonio Aguilar, Ines Bolle, Julia Calzada-WackClaudia Dalke, Nicole Ehrhardt, Jack Favor, Helmut Fuchs, Valérie Gailus-Durner, Wolfgang Hans, Gabriele Hölzlwimmer, Anahita Javaheri, Svetoslav Kalaydjiev, Magdalena Kallnik, Eva Kling, Sandra Kunder, Ilona Moßbrugger, Beatrix Naton, Ildikó Racz, Birgit Rathkolb, Jan Rozman, Anja Schrewe, Dirk H. Busch, Jochen Graw, Boris Ivandic, Martin Klingenspor, Thomas Klopstock, Markus Ollert, Leticia Quintanilla-Martinez, Holger Schulz, Eckhard Wolf, Wolfgang Wurst, Andreas Zimmer, Simon E. Fisher, Rudolf Morgenstern, Thomas Arendt, Martin Hrabé de Angelis, Julia Fischer, Johannes Schwarz, Svante Pääbo

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

392 Citations (Scopus)

Abstract

It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.

Original languageEnglish
Pages (from-to)961-971
Number of pages11
JournalCell
Volume137
Issue number5
DOIs
Publication statusPublished - 29 May 2009
Externally publishedYes

Keywords

  • EVO_ECOL
  • HUMDISEASE
  • SYSNEURO

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