Fmrp is required for the establishment of the startle response during the critical period of auditory development.
Fmrp is required for the establishment of the startle response during the critical period of auditory development.
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在听觉发育的关键时期建立惊吓反应需要 Fmrp。
DOI：
10.1016/j.brainres.2006.06.086
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发表时间：
2006
期刊：
影响因子：
2.9
通讯作者：
Toth,Miklos
中科院分区：
文献类型：
--
作者：
Yun,Seong-Wook;Platholi,Jimcy;Flaherty,MariaSol;Fu,Weimin;Kottmann,AndreasH;Toth,Miklos
脆性X综合征是遗传性智力低下的最常见形式，由FMR-1基因产物FMRP缺失引起。除了标志性的认知缺陷外，其他症状也很明显，包括多动、癫痫和感觉异常，包括对听觉、触觉、视觉和嗅觉刺激的敏感性增加。脆性X是一种发育障碍，第一症状在出生后第一年就显现出来，但人们对FMRP在发育过程中的作用知之甚少。脆性X的感觉高反应性可以在fmr-1基因敲除(KO)小鼠身上复制，明显表现为异常的听源性惊厥反应和听源性癫痫敏感性增加。在这里，我们研究了fmr-1KO小鼠在发育过程中惊恐缺陷的发生和出现。在出生后第2周末，野生型小鼠首次检测到惊吓反应。惊吓反应的幅度在出生后4周前显着增加，随后进一步但温和地增加到成年期。Fmr1基因在惊厥反应发生前和整个惊厥反应的整个发育过程中均可检测到表达。虽然直到出生后3-4周，fmr1 KO小鼠的惊吓反应的开始和幅度都没有改变，但超过这个年龄后，它不能进一步发展，导致成年KO小鼠的总体反应缺陷。这表明，虽然FMRP在惊吓反应发展的初始步骤中是可有可无的，但对于反应的充分发展是必要的。
Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the FMR-1 gene product FMRP. In addition to the hallmark cognitive defect, other symptoms are also apparent including hyperactivity, seizures and sensory abnormalities including a characteristic increase in sensitivity to auditory, tactile, visual, and olfactory stimuli. Fragile X is a developmental disorder with the first symptoms apparent in the first year of life but little is known about the role of FMRP in developmental processes. The sensory hyperreactivity of fragile X can be reproduced in fmr-1 knockout (KO) mice evident as abnormal audiogenic startle response and increased audiogenic seizure susceptibility. Here, we studied the onset and emergence of the startle deficit in fmr-1 KO mice during development. The startle response was first detectable at the end of the 2nd postnatal week in wild-type mice. The amplitude of startle response showed a substantial increase until the 4th postnatal week followed by a further but moderate increase up to adulthood. Expression of the fmr1 gene was detectable in the startle circuit before the onset and throughout the development of the startle response. Although the onset and amplitude of the startle response were not altered in fmr1 KO mice until the 3rd–4th postnatal week, beyond this age it failed to develop further resulting in an overall response deficit in adult KO mice. This indicates that although Fmrp is dispensable at the initial steps of startle response development, it is necessary for the full development of the response.