TY - JOUR
T1 - A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice
AU - Enard, Wolfgang
AU - Gehre, Sabine
AU - Hammerschmidt, Kurt
AU - Hölter, Sabine M.
AU - Blass, Torsten
AU - Somel, Mehmet
AU - Brückner, Martina K.
AU - Schreiweis, Christiane
AU - Winter, Christine
AU - Sohr, Reinhard
AU - Becker, Lore
AU - Wiebe, Victor
AU - Nickel, Birgit
AU - Giger, Thomas
AU - Müller, Uwe
AU - Groszer, Matthias
AU - Adler, Thure
AU - Aguilar, Antonio
AU - Bolle, Ines
AU - Calzada-Wack, Julia
AU - Dalke, Claudia
AU - Ehrhardt, Nicole
AU - Favor, Jack
AU - Fuchs, Helmut
AU - Gailus-Durner, Valérie
AU - Hans, Wolfgang
AU - Hölzlwimmer, Gabriele
AU - Javaheri, Anahita
AU - Kalaydjiev, Svetoslav
AU - Kallnik, Magdalena
AU - Kling, Eva
AU - Kunder, Sandra
AU - Moßbrugger, Ilona
AU - Naton, Beatrix
AU - Racz, Ildikó
AU - Rathkolb, Birgit
AU - Rozman, Jan
AU - Schrewe, Anja
AU - Busch, Dirk H.
AU - Graw, Jochen
AU - Ivandic, Boris
AU - Klingenspor, Martin
AU - Klopstock, Thomas
AU - Ollert, Markus
AU - Quintanilla-Martinez, Leticia
AU - Schulz, Holger
AU - Wolf, Eckhard
AU - Wurst, Wolfgang
AU - Zimmer, Andreas
AU - Fisher, Simon E.
AU - Morgenstern, Rudolf
AU - Arendt, Thomas
AU - Hrabé de Angelis, Martin
AU - Fischer, Julia
AU - Schwarz, Johannes
AU - Pääbo, Svante
N1 - Funding Information:
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 Schädler, Regina Kneuttinger, Bettina Sperling, Elfi Holupirek, Susanne Wittich, Elisabeth Schwarz, Miriam Backs, Eleonore Samson, Christine Führmann-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 für 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 für Wissenschaft und Kunst (M.K.B. and T.A.), the Interdisziplinärem Zentrum für 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.).
PY - 2009/5/29
Y1 - 2009/5/29
N2 - 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. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.
AB - 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. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.
KW - EVO_ECOL
KW - HUMDISEASE
KW - SYSNEURO
UR - http://www.scopus.com/inward/record.url?scp=65849256049&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2009.03.041
DO - 10.1016/j.cell.2009.03.041
M3 - Article
C2 - 19490899
AN - SCOPUS:65849256049
SN - 0092-8674
VL - 137
SP - 961
EP - 971
JO - Cell
JF - Cell
IS - 5
ER -