A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice
- Creators
- Enard, Wolfgang
- Gehre, Sabine
- Hammerschmidt, Kurt
- Hölter, Sabine M.
- Blass, Torsten
- Somel, Mehmet
- Brückner, Martina K.
- Schreiweis, Christiane
- Winter, Christine
- Sohr, Reinhard
- Becker, Lore
- Wiebe, Victor
- Nickel, Birgi
- Giger, Thomas
- Müller, Uwe
- Groszer, Matthias
- Adler, Thure
- Aguilar, Antonio
- Bolle, Ines
- Calzada-Wack, Julia
- Dalke, Claudia
- Ehrhardt, Nicole
- Favor, Jack
- Fuchs, Helmut
- Gailus-Durner, Valérie
- Hans, Wolfgang
- Hölzlwimmer, Gabriele
- Javaheri, Anahita
- Kalaydjiev, Svetoslav
- Kallnik, Magdalena
- Kling, Eva
- Kunder, Sandra
- Moßbrugger, Ilona
- Naton, Beatrix
- Racz, Ildikó
- 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 Hrabé
-
Fischer, Julia
- Schwarz, Johannes
- Pääbo, Svante
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.
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 http://www.cell.com/supplemental/S0092-8674(09)00378-X.Additional details
- Eprint ID
- 15751
- DOI
- 10.1016/j.cell.2009.03.041
- Resolver ID
- CaltechAUTHORS:20090911-075909920
- 01GS0850
- Bundesministerium fur Bildung und Forschung
- 01GS0851
- Bundesministerium fur Bildung und Forschung
- 01GS0852
- Bundesministerium fur Bildung und Forschung
- 01GS0869
- Bundesministerium fur Bildung und Forschung
- 01GS0853
- Bundesministerium fur Bildung und Forschung
- 01GS0854
- Bundesministerium fur Bildung und Forschung
- 01GS0868
- Bundesministerium fur Bildung und Forschung
- LSHG-2006-037188
- EU grant
- Deutsche Forschungsgemeinschaft
- Saxonian Staatsministerium fur Wissenschaft und Kunst
- Interdisziplinarem Zentrum fur Klinische Forschung in Leipzig
- Royal Society
- Max Planck Society
- Created
-
2009-10-02Created from EPrint's datestamp field
- Updated
-
2021-11-08Created from EPrint's last_modified field