Cell
Volume 137, Issue 5, 29 May 2009, Pages 961-971
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Article
A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice

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Summary

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.

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Present address: CAS-MPG Partner Institute for Computational Biology, SIBS, 320 Yue Yang Road, Shanghai, 200031, China

26

Present address: INSERM U 839, Institut du Fer à Moulin, University Pierre&Marie Curie, 17 rue du Fer à Moulin, 75005 Paris, France

27

Present address: Faculty of Life Sciences, AV Hill Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK

28

Present address: Infectious Diseases Program, Lovelace Respiratory Research Institute. 2425 Ridgecrest Dr. SE. Albuquerque, NM 87108, USA

29

Present address: Institut für Pathologie, University of Tuebingen, Liebermeisterstr. 8, 72076 Tuebingen, Germany