一种人源化版本的Foxp2会影响小鼠的皮质-基底神经节回路。
A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.
作者信息
Enard Wolfgang, Gehre Sabine, Hammerschmidt Kurt, Hölter Sabine M, Blass Torsten, Somel Mehmet, Brückner Martina K, Schreiweis Christiane, Winter Christine, Sohr Reinhard, Becker Lore, Wiebe Victor, Nickel Birgit, Giger Thomas, Müller Uwe, Groszer Matthias, Adler Thure, Aguilar Antonio, Bolle Ines, Calzada-Wack Julia, Dalke Claudia, Ehrhardt Nicole, Favor Jack, Fuchs Helmut, Gailus-Durner Valérie, Hans Wolfgang, Hölzlwimmer Gabriele, Javaheri Anahita, Kalaydjiev Svetoslav, Kallnik Magdalena, Kling Eva, Kunder Sandra, Mossbrugger Ilona, Naton Beatrix, Racz Ildikó, Rathkolb Birgit, Rozman Jan, Schrewe Anja, Busch Dirk H, Graw Jochen, Ivandic Boris, Klingenspor Martin, Klopstock Thomas, Ollert Markus, Quintanilla-Martinez Leticia, Schulz Holger, Wolf Eckhard, Wurst Wolfgang, Zimmer Andreas, Fisher Simon E, Morgenstern Rudolf, Arendt Thomas, de Angelis Martin Hrabé, Fischer Julia, Schwarz Johannes, Pääbo Svante
机构信息
Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany.
出版信息
Cell. 2009 May 29;137(5):961-71. doi: 10.1016/j.cell.2009.03.041.
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.
有人提出，转录因子FOXP2中的两个氨基酸替换在人类进化过程中由于对言语和语言方面的影响而受到正向选择。在这里，我们将这些替换引入小鼠的内源性Foxp2基因中。尽管这些小鼠总体健康，但它们的超声波发声在质量上有所不同，探索行为减少，大脑中的多巴胺浓度降低，这表明人源化的Foxp2等位基因会影响基底神经节。在纹状体中，基底神经节的一部分在由于无功能的FOXP2等位基因而存在言语缺陷的人类中受到影响，我们发现中等棘状神经元的树突长度增加，突触可塑性增强。由于携带一个无功能Foxp2等位基因的小鼠表现出相反的效果，这表明皮质 - 基底神经节回路中的改变可能对人类言语和语言的进化很重要。
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