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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-Wack | Claudia 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
Cell | 2009

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.

Pubmed ID: 19490899 RIS Download

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