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

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Cell 2009 May 29;137(5):961

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

Wiebe, V;Adler, T;Aguilar, A;Arendt, T;Becker, L;Blass, T;Bolle, I;Brückner, M;Busch, DH;Calzada-Wack, J;Dalke, C;Ehrhardt, N;Enard, W;Favor, J;Fischer, J;Fisher, SE;Fuchs, H;Gailus-Durner, V;Gehre, S;Giger, T;Graw, J;Groszer, M;Hammerschmidt, K;Hans, W;Hölter, S;Hölzlwimmer, G;Hrabé, de Angelis M;Ivandic, B;Javaheri, A;Kalaydjiev, S;Kallnik, M;Kling, E;Klingenspor, M;Klopstock, T;Kunder, S;Mobrugger, I;Morgenstern, R;Müller, U;Naton, B;Nickel, B;Ollert, M;Pääbo, S.;Quintanilla-Martinez, L;Racz, I;Rathkolb, B;Rozman, J;Schreiweis, C;Schrewe, A;Schulz, H;Schwarz, J;Sohr, R;Somel, M;Winter, C;Wolf, E;Wurst, W;Zimmer, A.

Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany

Service type: Humanized mice


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.

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