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

Date

2009-05-29

Author

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

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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.

Subject Keywords

Inherited speech, Language disorder, Ultrasonic vocalization, Synaptic plasticity, Brain-development, Gene, Gene, Evolution, Expression, Behavior, Identification

URI

https://hdl.handle.net/11511/35203

Journal

CELL

DOI

https://doi.org/10.1016/j.cell.2009.03.041

Collections

Department of Biology, Article

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Citation Formats

W. Enard et al., “A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice,” CELL, pp. 961–971, 2009, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/35203.