Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing.
Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing.
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DOI：
10.1093/cercor/bhx269
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发表时间：
2017-12-01
期刊：
影响因子：
--
通讯作者：
Molnár Z
中科院分区：
文献类型：
--
作者：
Guidi LG;Mattley J;Martinez-Garay I;Monaco AP;Linden JF;Velayos-Baeza A;Molnár Z
发展性阅读障碍是一种由遗传和非遗传因素引起的影响阅读能力的神经发育障碍。在迄今为止鉴定的易感基因中，KIAA 0319是主要候选基因。在大鼠中的RNA干扰实验表明其参与皮质迁移，但我们不能证实这些发现在Kiaa 0319突变小鼠。鉴于其同源基因Kiaa 0319 L（AU 040320）也被认为在神经元迁移中起作用，我们询问了单独或与KIAA 0319一起缺乏AU 040320是否会影响发育中大脑的迁移。对AU 040320和双Kiaa 0319; AU 040320敲除（dKO）的分析未发现皮质分层受损、神经元迁移、神经发生或其他解剖异常的证据。然而，dKO小鼠在行为噪声检测任务中表现出听觉缺陷。此外，点击诱发的听觉脑干反应的记录显示AU 040320-KO小鼠的III波振幅出现阈上缺陷，而dKO则出现更普遍的缺陷。这些发现表明，AU 040320的缺失破坏了听觉脑干的放电和/或活动同步，而这两种蛋白质的缺失可能会影响外周和中枢听觉功能。总体而言，这些结果与KIAA 0319和AU 040320在神经元迁移中的作用相反，并概述了它们与听觉系统缺陷的关系。
Developmental dyslexia is a neurodevelopmental disorder that affects reading ability caused by genetic and non-genetic factors. Amongst the susceptibility genes identified to date, KIAA0319 is a prime candidate. RNA-interference experiments in rats suggested its involvement in cortical migration but we could not confirm these findings in Kiaa0319-mutant mice. Given its homologous gene Kiaa0319L (AU040320) has also been proposed to play a role in neuronal migration, we interrogated whether absence of AU040320 alone or together with KIAA0319 affects migration in the developing brain. Analyses of AU040320 and double Kiaa0319;AU040320 knockouts (dKO) revealed no evidence for impaired cortical lamination, neuronal migration, neurogenesis or other anatomical abnormalities. However, dKO mice displayed an auditory deficit in a behavioral gap-in-noise detection task. In addition, recordings of click-evoked auditory brainstem responses revealed suprathreshold deficits in wave III amplitude in AU040320-KO mice, and more general deficits in dKOs. These findings suggest that absence of AU040320 disrupts firing and/or synchrony of activity in the auditory brainstem, while loss of both proteins might affect both peripheral and central auditory function. Overall, these results stand against the proposed role of KIAA0319 and AU040320 in neuronal migration and outline their relationship with deficits in the auditory system.
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影响因子：
3.7
作者：
Centanni TM;Chen F;Booker AM;Engineer CT;Sloan AM;Rennaker RL;LoTurco JJ;Kilgard MP
通讯作者：
Kilgard MP
影响因子：
3.7
作者：
Adler WT;Platt MP;Mehlhorn AJ;Haight JL;Currier TA;Etchegaray MA;Galaburda AM;Rosen GD
通讯作者：
Rosen GD
影响因子：
4.5
作者：
Dennis MY;Paracchini S;Scerri TS;Prokunina-Olsson L;Knight JC;Wade-Martins R;Coggill P;Beck S;Green ED;Monaco AP
通讯作者：
Monaco AP
影响因子：
16.2
作者：
Chandrasekaran, Bharath;Hornickel, Jane;Skoe, Erika;Nicol, Trent;Kraus, Nina
通讯作者：
Kraus, Nina
影响因子：
11.2
作者：
GALABURDA, AM;KEMPER, TL
通讯作者：
KEMPER, TL