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

Enard, Wolfgang and Gehre, Sabine and Hammerschmidt, Kurt and Hölter, Sabine M. and Blass, Torsten and Somel, Mehmet and Brückner, Martina K. and Schreiweis, Christiane and Winter, Christine and Sohr, Reinhard and Becker, Lore and Wiebe, Victor and Nickel, Birgi and Giger, Thomas and Müller, Uwe and Groszer, Matthias and Adler, Thure and Aguilar, Antonio and Bolle, Ines and Calzada-Wack, Julia and Dalke, Claudia and Ehrhardt, Nicole and Favor, Jack and Fuchs, Helmut and Gailus-Durner, Valérie and Hans, Wolfgang and Hölzlwimmer, Gabriele and Javaheri, Anahita and Kalaydjiev, Svetoslav and Kallnik, Magdalena and Kling, Eva and Kunder, Sandra and Moßbrugger, Ilona and Naton, Beatrix and Racz, Ildikó and Rathkolb, Birgit and Rozman, Jan and Schrewe, Anja and Busch, Dirk H. and Graw, Jochen and Ivandic, Boris and Klingenspor, Martin and Klopstock, Thomas and Ollert, Markus and Quintanilla-Martinez, Leticia and Schulz, Holger and Wolf, Eckhard and Wurst, Wolfgang and Zimmer, Andreas and Fisher, Simon E. and Morgenstern, Rudolf and Arendt, Thomas and de Angelis, Martin Hrabé and Fischer, Julia and Schwarz, Johannes and Pääbo, Svante (2009) A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice. Cell, 137 (5). pp. 961-971. ISSN 0092-8674.

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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.

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Fischer, Julia0000-0001-6697-7808
Additional Information:© 2009 Elsevier B.V. Received 30 April 2008; revised 27 January 2009; accepted 17 March 2009. Published: May 28, 2009. Available online 28 May 2009. We are grateful to Ozgene Inc. for generating mice; to Uta Zirkler (MPI-EVA) for animal care; to Reinhard Seeliger and the German Mouse Clinic technician team (Maria Kugler, Tamara Halex, Claudia Zeller, Sandra Scha¨ dler, Regina Kneuttinger, Bettina Sperling, Elfi Holupirek, Susanne Wittich, Elisabeth Schwarz, Miriam Backs, Eleonore Samson, Christine Fu¨ hrmann-Franz, and Kerstin Kutzner) and the animal caretaker team for expert technical help; to Eunjong Park (MPI-EVA, Neurology Leipzig) for assistance in neuronal cell culture; to Sven-Holger Puppel and Sabrina Reimers (MPI-EVA) for assistance in generating expression data; and to Christine Green (MPI-EVA) for comments on the manuscript. This work was supported by NGFNplus grants from the Bundesministerium fu¨ r Bildung und Forschung (01GS0850 (I.B., C.C.-W., C.D., J.F., H.F., V.G.-D., W.H., G.H., M.K., S.K., I.M., B.,N., J.G., L.Q.-M., H.S., W.W., and M.H.A), 01GS0851 (L.B., B.R. C.M., E.K., E.W. and Th.K.), 01GS0852 (T.A., S.K., and D.B.), 01GS0869 (N.E., J.R., and M.K.), 01GS0853 (I.R. and A.Z.), 01GS0854 (A.S. and B.I.), 01GS0868 (A.A., A.J., and M.O.), by an EU grant (EUMODIC LSHG-2006-037188, German Mouse Clinic), grants from the Deutsche Forschungsgemeinschaft (S.G. and J.S., M.K.B. and T.A., Heisenberg grant to J.F.), the Saxonian Staatsministerium fu¨ r Wissenschaft und Kunst (M.K.B. and T.A.), the Interdisziplina¨ rem Zentrum fu¨ r Klinische Forschung in Leipzig (TP C27 to S.G. and J.S.), the Royal Society (research fellowship to S.E.F.), and the Max Planck Society (W.E. and S.P.). SUPPLEMENTAL DATA Supplemental Data include Supplemental Experimental Procedures, nine tables, nine figures, and a video summary and can be found with this article online at
Funding AgencyGrant Number
Bundesministerium fur Bildung und Forschung01GS0850
Bundesministerium fur Bildung und Forschung01GS0851
Bundesministerium fur Bildung und Forschung01GS0852
Bundesministerium fur Bildung und Forschung01GS0869
Bundesministerium fur Bildung und Forschung01GS0853
Bundesministerium fur Bildung und Forschung01GS0854
Bundesministerium fur Bildung und Forschung01GS0868
EU grantLSHG-2006-037188
Deutsche ForschungsgemeinschaftUNSPECIFIED
Saxonian Staatsministerium fur Wissenschaft und KunstUNSPECIFIED
Interdisziplinarem Zentrum fur Klinische Forschung in LeipzigUNSPECIFIED
Max Planck SocietyUNSPECIFIED
Issue or Number:5
Record Number:CaltechAUTHORS:20090911-075909920
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15751
Deposited By: Tony Diaz
Deposited On:02 Oct 2009 18:21
Last Modified:09 Mar 2020 13:18

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