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

被引：361

作者：

Enard, Wolfgang ^{[1
]}

Gehre, Sabine ^{[1
]}

Hammerschmidt, Kurt ^{[2
]}

Hoelter, Sabine M. ^{[3
]}

Blass, Torsten ^{[1
]}

Somel, Mehmet ^{[1
]}

Brueckner, Martina K. ^{[4
]}

Schreiweis, Christiane ^{[1
]}

Winter, Christine ^{[5
]}

Sohr, Reinhard ^{[6
]}

Becker, Lore ^{[7
,8
]}

Wiebe, Victor ^{[1
]}

Nickel, Birgit ^{[1
]}

Giger, Thomas ^{[1
]}

Mueller, Uwe ^{[9
]}

Groszer, Matthias ^{[10
]}

Adler, Thure ^{[8
,11
]}

Aguilar, Antonio ^{[12
]}

Bolle, Ines ^{[13
]}

Calzada-Wack, Julia ^{[14
]}

Dalke, Claudia ^{[3
]}

Ehrhardt, Nicole ^{[8
,15
]}

Favor, Jack ^{[16
]}

Fuchs, Helmut ^{[8
]}

Gailus-Durner, Valerie ^{[8
]}

Hans, Wolfgang ^{[8
]}

Hoelzlwimmer, Gabriele ^{[14
]}

Javaheri, Anahita ^{[8
,12
]}

Kalaydjiev, Svetoslav ^{[11
]}

Kallnik, Magdalena ^{[3
]}

Kling, Eva ^{[7
,8
]}

Kunder, Sandra ^{[14
]}

Mossbrugger, Ilona ^{[14
]}

Naton, Beatrix ^{[8
]}

Racz, Ildiko ^{[17
]}

Rathkolb, Birgit ^{[8
,18
]}

Rozman, Jan ^{[8
,20
,21
]}

Schrewe, Anja ^{[8
,19
]}

Busch, Dirk H. ^{[11
]}

Graw, Jochen ^{[3
]}

Ivandic, Boris ^{[19
]}

Klingenspor, Martin ^{[20
,21
]}

Klopstock, Thomas ^{[7
]}

Ollert, Markus ^{[12
]}

Quintanilla-Martinez, Leticia ^{[14
]}

Schulz, Holger ^{[13
]}

Wolf, Eckhard ^{[18
]}

Wurst, Wolfgang ^{[3
,22
]}

Zimmer, Andreas ^{[17
]}

Fisher, Simon E. ^{[10
]}

机构：

[1] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany

[2] German Primate Ctr, Dept Cognit Ethol, D-37077 Gottingen, Germany

[3] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Dev Genet, D-85764 Munich, Germany

[4] Univ Leipzig, Paul Flechsig Inst Brain Res, Dept Neuroanat, D-04109 Leipzig, Germany

[5] Univ Med Berlin, Charite Campus Mitte, Dept Psychiat & Psychotherapy, Berlin, Germany

[6] Univ Med Berlin, Charite Campus Mitte, Inst Pharmacol & Toxicol, Berlin, Germany

[7] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-8000 Munich, Germany

[8] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Expt Genet, D-85764 Munich, Germany

[9] Univ Leipzig, Inst Immunol, BBZ, D-04103 Leipzig, Germany

[10] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[11] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany

[12] Tech Univ Munich, Dept Dermatol & Allergy, Div Environm Dermatol & Allergy TUM HMGU, D-80802 Munich, Germany

[13] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Lung Biol & Dis, D-85764 Munich, Germany

[14] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Pathol, D-85764 Munich, Germany

[15] Univ Marburg, Fac Biol, D-35032 Marburg, Germany

[16] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Munich, Germany

[17] Univ Bonn, Life & Brain Ctr, Dept Mol Psychiat, D-53105 Bonn, Germany

[18] Univ Munich, Gene Ctr, Inst Mol Anim Breeding & Biotechnol, D-81377 Munich, Germany

[19] Heidelberg Univ, Dept Med 3, Div Cardiol, D-69120 Heidelberg, Germany

[20] Tech Univ Munich, Else Kroner Fresenius Ctr, D-85350 Freising Weihenstephan, Germany

[21] Res Ctr Nutr & Food Sci, ZIEL, D-85350 Freising Weihenstephan, Germany

[22] Max Planck Inst Psychiat, D-80804 Munich, Germany

[23] Tech Univ Munich, Lehrstuhl Expt Genet, D-85350 Freising Weihenstephan, Germany

[24] Univ Leipzig, Dept Neurol, D-04103 Leipzig, Germany

[25] CALTECH, Div Biol 156 29, Pasadena, CA 91125 USA

来源：

CELL | 2009年 / 137卷 / 05期

关键词：

INHERITED SPEECH; LANGUAGE DISORDER; ULTRASONIC VOCALIZATION; SYNAPTIC PLASTICITY; BRAIN-DEVELOPMENT; GENE; EVOLUTION; EXPRESSION; BEHAVIOR; IDENTIFICATION;

D O I：

10.1016/j.cell.2009.03.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Paper-Flick file available with the online Supplemental Data.

引用

页码：961 / 971

页数：11

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