2012年9月8日 讯 /生物谷BIOON/ --当小鼠在出生时缺少主基因Atoh1,就会在刚出生阶段不能呼吸,最终死亡。这种情况发生的原因或许为我们解答了婴儿猝死综合症(sudden infant death syndrome,SIDS)的发生原因。目前来自贝勒医学院和德克萨斯儿童医院的研究者揭示了,当在一种称为RTN(retrotrapezoid nucleus,斜方体后核)的特殊神经元中缺少Atoh1基因时,大约一半的新出生小鼠会死亡。那些勉强生存下来的小鼠也会变得对过度水平的二氧化碳不敏感。这项研究报告刊登在了近日的国际杂志Neuron上。
新生小鼠的死亡暗示我们,基因Atoh1对于维持新生儿呼吸的神经元非常关键,因此,研究者开始对这些特殊神经元进行深入研究。研究者使用了一种遗传学方法来寻找这些关键神经元,当对大脑狭窄区域的基因进行敲除后,研究者慢慢排除了决定RTN神经元中Atoh1缺失的神经元是新生小鼠为何死亡的原因。
研究者Zoghbi表示,发现Atoh1的确对于RTN神经元在脑干和呼吸中心建立联系并且进行合适定位非常关键,这也帮助我们揭开了为什么这些东西对于新生儿呼吸非常重要。神经元常常会定位在腹侧脑干中,当血液中组分发生改变(缺少氧气或者二氧化碳增多)时,RTN神经元就会迅速感知并且告知机体对呼吸做出改变。但是如果神经元有缺失的话便会严重影响这一系列反应。
在小鼠中缺失Atoh1基因将会给其带来严重的呼吸问题,因为小鼠并不会自动调节呼吸来降低血液中二氧化碳的摄入和增加氧气的供给。相关研究资助由美国心脏协会西南协会提供。(生物谷Bioon.com)
编译自:Master Gene Affects Neurons That Govern Breathing at Birth and in Adulthood
doi:10.1016/j.neuron.2012.06.027
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Atoh1 Governs the Migration of Postmitotic Neurons that Shape Respiratory Effectiveness at Birth and Chemoresponsiveness in Adulthood
Wei-Hsiang Huang, Srinivasan Tupal, Teng-Wei Huang, Christopher S. Ward, Jeffery L. Neul, Tiemo J. Klisch, Paul A. Gray, Huda Y. Zoghbi
Hindbrain neuronal networks serving respiratory, proprioceptive, and arousal functions share a developmental requirement for the bHLH transcription factor Atoh1. Loss of Atoh1 in mice results in respiratory failure and neonatal lethality; however, the neuronal identity and mechanism by which Atoh1-dependent cells sustain newborn breathing remains unknown. We uncovered that selective loss of Atoh1 from the postmitotic retrotrapezoid nucleus (RTN) neurons results in severely impaired inspiratory rhythm and pronounced neonatal death. Mice that escape neonatal death develop abnormal chemoresponsiveness as adults. Interestingly, the expression of Atoh1 in the RTN neurons is not required for their specification or maintenance, but is important for their proper localization and to establish essential connections with the preBötzinger Complex (preBötC). These results provide insights into the genetic regulation of neonatal breathing and shed light on the labile sites that might contribute to sudden death in newborn infants and altered chemoresponsiveness in adults.