Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits.
Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits.
复制标题
DOI：
10.1016/j.cub.2008.01.060
复制
发表时间：
2008-03-11
期刊：
影响因子：
9.2
通讯作者：
Fisher, Simon E.
中科院分区：
文献类型：
--
作者：
Groszer, Matthias;Keays, David A.;Deacon, Robert M. J.;de Bono, Joseph P.;Prasad-Mulcare, Shweta;Gaub, Simone;Baum, Muriel G.;French, Catherine A.;Nicod, Jrme;Coventry, Julie A.;Enard, Wolfgang;Fray, Martin;Brown, Steve D. M.;Nolan, Patrick M.;Paeaebo, Svante;Channon, Keith M.;Costa, Rui M.;Eilers, Jens;Ehret, Guenter;Nicholas, J.;Rawlins, P.;Fisher, Simon E.
遗传性言语和语言障碍最详尽描述的例子是在多代KE家族中观察到的情况，它是由FOXP2基因的杂合错义突变引起的。受影响的个体的特征是在学习和产生构成流利言语基础的复杂口面部运动序列方面存在缺陷，并且在口语和书面语言的语言处理方面都表现出受损。FOXP2转录因子在许多脊椎动物物种中高度相似，在与感觉运动整合和运动学习相关的神经回路中具有保守的表达。在这项研究中，我们培育出了携带与KE家族相同点突变的小鼠，在Foxp2 DNA结合域产生了等效的精氨酸到组氨酸的替换。纯合子R552H小鼠显示出小脑生长和出生后体重增加严重减少，但能够发出复杂的先天性超声发声。杂合子R552H小鼠在大脑结构和发育方面明显正常。关键的是，尽管它们的基线运动能力似乎与野生型同窝小鼠相同，但R552H杂合子在物种典型的运动技能学习方面表现出显著缺陷，同时在纹状体和小脑神经回路中伴有异常的突触可塑性。
The most well-described example of an inherited speech and language disorder is that observed in the multigenerational KE family, caused by a heterozygous missense mutation in the FOXP2 gene. Affected individuals are characterized by deficits in the learning and production of complex orofacial motor sequences underlying fluent speech and display impaired linguistic processing for both spoken and written language. The FOXP2 transcription factor is highly similar in many vertebrate species, with conserved expression in neural circuits related to sensorimotor integration and motor learning. In this study, we generated mice carrying an identical point mutation to that of the KE family, yielding the equivalent arginine-to-histidine substitution in the Foxp2 DNA-binding domain. Homozygous R552H mice show severe reductions in cerebellar growth and postnatal weight gain but are able to produce complex innate ultrasonic vocalizations. Heterozygous R552H mice are overtly normal in brain structure and development. Crucially, although their baseline motor abilities appear to be identical to wild-type littermates, R552H heterozygotes display significant deficits in species-typical motor-skill learning, accompanied by abnormal synaptic plasticity in striatal and cerebellar neural circuits.
登录
查看更多内容
影响因子：
105.7
作者：
MATTHEWS, JNS;ALTMAN, DG;ROYSTON, P
通讯作者：
ROYSTON, P
影响因子：
2.6
作者：
Ehret, G
通讯作者：
Ehret, G
影响因子：
--
作者：
Middleton, FA;Strick, PL
通讯作者：
Strick, PL
影响因子：
25
作者：
Gerdeman, GL;Ronesi, J;Lovinger, DM
通讯作者：
Lovinger, DM
影响因子：
30.8
作者：
Coghill, EL;Hugill, A;Brown, SDM
通讯作者：
Brown, SDM