Altered social behavior in mice carrying a cortical Foxp2 deletion.
Altered social behavior in mice carrying a cortical Foxp2 deletion.
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皮质 Foxp2 缺失的小鼠的社会行为发生改变。
DOI：
10.1093/hmg/ddy372
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发表时间：
2019
影响因子：
3.5
通讯作者：
Groszer,Matthias
中科院分区：
文献类型：
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作者：
Medvedeva,VeraP;Rieger,MichaelA;Vieth,Beate;Mombereau,Cédric;Ziegenhain,Christoph;Ghosh,Tanay;Cressant,Arnaud;Enard,Wolfgang;Granon,Sylvie;Dougherty,JosephD;Groszer,Matthias
人类叉头盒转录因子FOXP2的遗传中断会导致常染色体显性言语和语言障碍。虽然FOXP的表达模式高度保守，但它在哺乳动物特定脑区对社会行为的作用在很大程度上仍不清楚。在这里，我们研究了携带皮质Foxp2纯合子缺失的小鼠。突变小鼠的出生后发育和大体形态结构与野生型(WT)小鼠没有区别。对成年小鼠的无偏见行为分析显示，在接近同种特定的行为以及WT互动伙伴的互惠反应方面存在异常。此外，突变小鼠的超声波发声的声学参数也发生了变化，这在社会背景下的作用也不同。皮质锥体神经元的细胞类型特异性基因表达谱揭示了参与社会行为的基因的异常调节。特别是，Foxp2突变体显示了Mint2(Apba2)的下调，这是一种与小鼠接近行为和人类自闭症谱系障碍有关的基因。综上所述，这些数据表明，小鼠的正常社会行为需要皮质Foxp2。
Genetic disruptions of the forkhead box transcription factor FOXP2 in humans cause an autosomal-dominant speech and language disorder. WhileFOXP2expression pattern are highly conserved, its role in specific brain areas for mammalian social behaviors remains largely unknown. Here we studied mice carrying a homozygous corticalFoxp2deletion. The postnatal development and gross morphological architecture of mutant mice was indistinguishable fromwildtype(WT) littermates. Unbiased behavioral profiling of adult mice revealed abnormalities in approach behavior towards conspecifics as well as in the reciprocal responses of WT interaction partners. Furthermore mutant mice showed alterations in acoustical parameters of ultrasonic vocalizations, which also differed in function of the social context. Cell type-specific gene expression profiling of cortical pyramidal neurons revealed aberrant regulation of genes involved in social behavior. In particularFoxp2mutants showed the downregulation ofMint2 (Apba2), a gene involved in approach behavior in mice and autism spectrum disorder in humans. Taken together these data demonstrate that cortical Foxp2 is required for normal social behaviors in mice.