Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression in striatums of Foxp2-hum, Foxp2-ko and wild-type 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 an effect of the humanized Foxp2 allele on basal ganglia. In the striatum, a part of the basal ganglia that is affected in humans with a speech deficit due to one non-functional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one non-functional 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. In this particular experiment, we investigate the effects of human Foxp2 (Foxp2hum) and the non-functional Foxp2 allele on striatal gene expression in embryonic, young and adult mice. We determined genome-wide gene expression patterns in striatal biopsies from Foxp2hum/hum, Foxp2wt/ko and Foxp2wt/wt mice using high-density oligonucleotide arrays. The animals were derived from two independent FoxP2 knock-in strains and one knock-out strain. In total 71 animals were used, 29 males and 42 females. The mice ages were E16.5, P15, P18, P21 and P95 when sacrificed. The microarrays were processed in totally six batches.

ORGANISM(S): Mus musculus

SUBMITTER: Lore Becker 

PROVIDER: E-GEOD-13588 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.

Enard Wolfgang W   Gehre Sabine S   Hammerschmidt Kurt K   Hölter Sabine M SM   Blass Torsten T   Somel Mehmet M   Brückner Martina K MK   Schreiweis Christiane C   Winter Christine C   Sohr Reinhard R   Becker Lore L   Wiebe Victor V   Nickel Birgit B   Giger Thomas T   Müller Uwe U   Groszer Matthias M   Adler Thure T   Aguilar Antonio A   Bolle Ines I   Calzada-Wack Julia J   Dalke Claudia C   Ehrhardt Nicole N   Favor Jack J   Fuchs Helmut H   Gailus-Durner Valérie V   Hans Wolfgang W   Hölzlwimmer Gabriele G   Javaheri Anahita A   Kalaydjiev Svetoslav S   Kallnik Magdalena M   Kling Eva E   Kunder Sandra S   Mossbrugger Ilona I   Naton Beatrix B   Racz Ildikó I   Rathkolb Birgit B   Rozman Jan J   Schrewe Anja A   Busch Dirk H DH   Graw Jochen J   Ivandic Boris B   Klingenspor Martin M   Klopstock Thomas T   Ollert Markus M   Quintanilla-Martinez Leticia L   Schulz Holger H   Wolf Eckhard E   Wurst Wolfgang W   Zimmer Andreas A   Fisher Simon E SE   Morgenstern Rudolf R   Arendt Thomas T   de Angelis Martin Hrabé MH   Fischer Julia J   Schwarz Johannes J   Pääbo Svante S  

Cell 20090501 5


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 a  ...[more]

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