A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice
A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice
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DOI：
10.1016/j.cell.2009.03.041
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发表时间：
2009-05-29
期刊：
影响因子：
64.5
通讯作者：
Paeaebo, Svante
中科院分区：
文献类型：
--
作者：
Enard, Wolfgang;Gehre, Sabine;Paeaebo, Svante
已经提出，转录因子FOXP2中的两个氨基酸取代在人类进化过程中由于对言语和语言方面的影响而被积极选择。在这里，我们将这些取代引入小鼠的内源性Foxp2基因。虽然这些小鼠通常是健康的，但它们具有性质上不同的超声发声，探索行为减少和脑中多巴胺浓度降低，表明人源化Foxp2等位基因影响基底神经节。在纹状体，一部分的基底神经节的影响，在人类的语言缺陷，由于一个非功能性FOXP2等位基因，我们发现，中型多刺神经元树突长度增加和突触可塑性增加。由于携带一个非功能性Foxp2等位基因的小鼠表现出相反的效果，这表明皮质基底神经节回路的改变可能对人类语音和语言的进化很重要。
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.