title: A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.
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.
authors.affiliation: Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany. enard@eva.mpg.de
authors.forename: Wolfgang
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authors.lastname: Enard
authors.forename: Sabine
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authors.lastname: Gehre
authors.forename: Kurt
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authors.lastname: Hammerschmidt
authors.forename: Sabine M
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authors.forename: Christiane
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authors.forename: Christine
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authors.lastname: Winter
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authors.lastname: Adler
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authors.lastname: Aguilar
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authors.lastname: Bolle
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authors.forename: Claudia
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authors.forename: Jack
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authors.forename: Wolfgang
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authors.forename: Gabriele
authors.initials: G
authors.lastname: Hölzlwimmer
authors.forename: Anahita
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authors.lastname: Javaheri
authors.forename: Svetoslav
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authors.lastname: Kalaydjiev
authors.forename: Magdalena
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authors.lastname: Kallnik
authors.forename: Eva
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authors.lastname: Kling
authors.forename: Sandra
authors.initials: S
authors.lastname: Kunder
authors.forename: Ilona
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authors.lastname: Mossbrugger
authors.forename: Beatrix
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authors.lastname: Naton
authors.forename: Ildikó
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authors.lastname: Racz
authors.forename: Birgit
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authors.lastname: Rathkolb
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Anja
authors.initials: A
authors.lastname: Schrewe
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
authors.forename: Boris
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authors.lastname: Ivandic
authors.forename: Martin
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authors.lastname: Klingenspor
authors.forename: Thomas
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authors.lastname: Klopstock
authors.forename: Markus
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authors.lastname: Ollert
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Andreas
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authors.lastname: Zimmer
authors.forename: Simon E
authors.initials: SE
authors.lastname: Fisher
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morgenstern
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Julia
authors.initials: J
authors.lastname: Fischer
authors.forename: Johannes
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authors.lastname: Schwarz
authors.forename: Svante
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authors.lastname: Pääbo
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D005075:Biological Evolution; D003712:Dendrites / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007802:Language; D036881:Long-Term Synaptic Depression; D051379:Mice; D009434:Neural Pathways; D009473:Neuronal Plasticity; D013060:Speech; D014828:Vocalization, Animal
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D004298:Dopamine