Foxp2小鼠模型中发育性言语障碍的分子遗传学研究

doi:10.3969/j.issn.1674-5817.2019.04.015

实验动物与比较医学 ›› 2019, Vol. 39 ›› Issue (4): 331-336.DOI: 10.3969/j.issn.1674-5817.2019.04.015

• 综述 • 上一篇

Foxp2小鼠模型中发育性言语障碍的分子遗传学研究

李慧

北京师范大学珠海分校, 珠海 519080

收稿日期:2019-03-28 出版日期:2019-08-25 发布日期:2021-01-31
作者简介:李慧,北京师范大学珠海分校副教授,硕士。研究方向为神经语言学、生物语言学。E-mail:huisp@163.com
基金资助:
北京师范大学珠海分校“创新强校”科研项目(201771023)

Molecular Genetical Research of Developmental Language Disorders in Foxp2 Mouse Models

LI Hui

Beijing Normal University at Zhuhai Campus, Zhuhai 519080, China

Received:2019-03-28 Online:2019-08-25 Published:2021-01-31

摘要/Abstract

摘要： 叉头框P2基因(FOXP2)是第一例发现的与一种特异性言语和语言障碍,即发育性言语失用症相关的基因。这一发现开启了研究相关神经通路的崭新方向。FOXP2在各种脊椎动物中显示了序列和神经系统表达的显著高度保守性,例如它在人胎脑中与对等阶段的小鼠胎脑中表达模式高度相似。Foxp2小鼠模型包括基因敲除鼠,类似KE家族病理突变的鼠以及Foxp2被人源化的鼠。本文将从分子网络、感觉处理、运动技能学习等三方面综述对Foxp2小鼠模型的研究,以阐明语言障碍的遗传基础。

关键词: 叉头框P2基因(FOXP2), 发育性言语失用症, Foxp2小鼠模型, 神经通路

Abstract: FOXP2 was the first gene discovered to be related to a fairly specific speech and language phenotype, called developmental verbal dyspraxia (DVD). This mechanism discovery opened up a new direction for the research of the relevant neural pathway. FOXP2 showed significantly high conservation of sequence and expression in the neural system of a variety of vertebrates, one typical example was that the expression patterns in human fetal brains were highly similar to those in mice of a comparable embryonic stage. Foxp2 mouse models include knock-out mice, mice that carry the etiological mutations that mirror those of the KE family or other patients, and mice in which the murine Foxp2 gene has been ‘humanized’ by including the two human-specific amino acids. The study of the Foxp2 mouse models was reviewed in this paper from molecular networks, sensory processing and motor skill learning, which aimed to shed light on the genetical mechanism of the language disorders.

Key words: Forkhead box P2 (FOXP2), Developmental verbal dyspraxia (DVD)

中图分类号:

R338
Q189

李慧. Foxp2小鼠模型中发育性言语障碍的分子遗传学研究[J]. 实验动物与比较医学, 2019, 39(4): 331-336.

LI Hui. Molecular Genetical Research of Developmental Language Disorders in Foxp2 Mouse Models[J]. Laboratory Animal and Comparative Medicine, 2019, 39(4): 331-336.

参考文献

[1] Reuter MS, Riess A, Moog U, et al.FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum[J]. J Med Genet, 2017, 54(1):64-72.
[2] Constance S, Jana P.Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language[J]. Philos Trans R Soc Lond B Biol Sci, 2011, 366(1574):2124-2140.
[3] Liegeois F, Morgan AT, Connelly A, et al.Endophenotypes of FOXP2: dysfunction within the human articulatory network[J]. Eur J Paediatr Neurol, 2011, 15(4):283-288.
[4] Deriziotis P, Fisher SE.Speech and language: translating the genome[J]. Trends Genet, 2017, 33(9):642-656.
[5] Turner SJ, Hildebrand MS, Block S, et al.Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria[J]. Am J Med Genet A, 2013, 161:2321-2326.
[6] Campbell P, Reep RL, Stoll ML, et al.Conservation and diversity of Foxp2 expression in muroid rodents: functional implications[J]. J Comp Neurol, 2009, 512(1):84-100.
[7] Gaub S, Fisher SE, Ehret G, et al.Ultrasonic vocalizations of adult male Foxp2-mutant mice: behavioral contexts of arousal and emotion[J]. Genes Brain Behav, 2016,15(2):243-59.
[8] Chabout J, Sarkar A, Patel SR, et al.A Foxp2 mutation implicated in human speech deficits alters sequencing of ultrasonic vocalizations in adult male mice[J]. Front Behav Neurosci, 2016,10:197.
[9] Vernes SC, Oliver PL, Spiteri E, et al.Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain[J]. PLoS Genet, 2011, 7(7):e1002145.
[10] Clovis Y, Enard W, Hutiner W, et al.Convergent repression of Foxp2 3’ UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons[J]. Development, 2012, 139(18):3332-3342.
[11] Toma C, Pierce KD, Shaw AD, et al.Comprehensive cross-disorder analyses of CNTNAP2 suggest it is unlikely to be a primary risk gene for psychiatric disorders[J]. PLoS Genet, 2018, 14(12):e1007535.
[12] Sia G, Clem R, Huganir R, et al.The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice[J]. Science, 2013, 342(6161):987-991.
[13] Soteros B, Cong Q, Palmer C, et al.Sociability and synapse subtype-specific defects in mice lacking SRPX2, a language-associated gene[J]. PLoS One, 2018,13(6): e0199399.
[14] Chen Y, Kuo H, Bornschein U, et al.Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c[J]. Nat Neurosci, 2016,19(11):1513-1522.
[15] Medvedeva V, Rieger M, Vieth B.Altered social behavior in mice carrying a cortical Foxp2 deletion[J]. Hum Mol Genet, 2018, doi: 10.1093.
[16] Kurt S, Groszer M, Fisher SE, et al.Modified sound-evoked brainstem potentials in Foxp2 mutant mice[J]. Brain Res, 2009, 1289(5):30-36.
[17] Kurt S, Fisher SE, Ehret G.Foxp2 mutations impair auditory-motor association learning[J]. PLoS One, 2012, 7(3):e33130.
[18] Heiman M, Schaefer A, Gong S, et al.A translational profiling approach for the molecular characterization of CNS cell types[J]. Cell, 2008, 135(4):738-748.
[19] Groszer M, Keays DA, Deacon RM, et al.Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits[J]. Curr Biol, 2008, 18(5):354-362.
[20] Enard W, Gehre S, Hammerschmidt K, et al.A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice[J]. Cell, 2009, 137(5):961-971.
[21] French C, Jin X, Campbell T, et al.An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning[J]. Mol Psychiatry, 2011, 17(11):1077-1085.
[22] van R, Fisher S, Vernes S, et al. Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release[J]. Brain Struct Funct, 2018, 223(9):4211-4226.
[23] Schreiweis C, Bornschein U, Burguiere E,, et al.Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance[J]. Proc Natl Acad Sci U S A, 2014, 111(39):14253-14258.
[24] Schreiweis C, Irinopoulou T, Vieth B, et al. Mice carrying a humanized Foxp2 knock-in allele show region-specific shifts of striatal Foxp2 expression levels[J]. Cortex, 2019, pii: S0010-9452(19)30027-9.
[25] Hammerschmidt K, Schreiweis C, Minge C, et al.A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice[J]. Genes Brain Behav, 2015,14(8):583-590.
[26] Usui N, Co M, Harper M, et al.Sumoylation of FOXP2 regulates motor function and vocal communication through purkinje cell development[J]. Biol Psychiatry, 2017, 81(3):220-230.
[27] Castellucci G, McGinley M, McCormick D. Knockout of Foxp2 disrupts vocal development in mice[J]. Sci Rep, 2016, 6:23305.
[28] Shi Z, Piccus Z, Zhang X, et al. miR-9 regulates basal ganglia-dependent developmental vocallearning and adult vocal performance in songbirds [J]. Elife, 2018,7:pii:e29087.
[29] Adam I, Mendoza E, Kobalz U, et al.CNTNAP2 is a direct FoxP2 target in vitro and in vivo in zebra finches: complex regulation by age and activity[J]. Genes Brain Behav, 2016,16(6):635-642.
[30] Xu S, Liu P, Chen Y.et al.Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion[J]. Proc Natl Acad Sci U S A, 2018, 115(35):8799-8804.
[31] Takahashi D, Fenley A, Teramoto Y, et al.Language development. The developmental dynamics of marmoset monkey vocal production[J]. Science, 2015, 349(6249):734-738.

Foxp2小鼠模型中发育性言语障碍的分子遗传学研究

Molecular Genetical Research of Developmental Language Disorders in Foxp2 Mouse Models

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