2012年9月8日 訊 /生物谷BIOON/ --當(dāng)小鼠在出生時(shí)缺少主基因Atoh1,，就會(huì)在剛出生階段不能呼吸，最終死亡,。這種情況發(fā)生的原因或許為我們解答了嬰兒猝死綜合癥（sudden infant death syndrome,，SIDS）的發(fā)生原因。目前來(lái)自貝勒醫(yī)學(xué)院和德克薩斯兒童醫(yī)院的研究者揭示了,，當(dāng)在一種稱為RTN(retrotrapezoid nucleus,，斜方體后核)的特殊神經(jīng)元中缺少Atoh1基因時(shí),，大約一半的新出生小鼠會(huì)死亡。那些勉強(qiáng)生存下來(lái)的小鼠也會(huì)變得對(duì)過(guò)度水平的二氧化碳不敏感,。這項(xiàng)研究報(bào)告刊登在了近日的國(guó)際雜志Neuron上,。
新生小鼠的死亡暗示我們，基因Atoh1對(duì)于維持新生兒呼吸的神經(jīng)元非常關(guān)鍵,，因此,，研究者開始對(duì)這些特殊神經(jīng)元進(jìn)行深入研究,。研究者使用了一種遺傳學(xué)方法來(lái)尋找這些關(guān)鍵神經(jīng)元,，當(dāng)對(duì)大腦狹窄區(qū)域的基因進(jìn)行敲除后，研究者慢慢排除了決定RTN神經(jīng)元中Atoh1缺失的神經(jīng)元是新生小鼠為何死亡的原因,。
研究者Zoghbi表示,，發(fā)現(xiàn)Atoh1的確對(duì)于RTN神經(jīng)元在腦干和呼吸中心建立聯(lián)系并且進(jìn)行合適定位非常關(guān)鍵，這也幫助我們揭開了為什么這些東西對(duì)于新生兒呼吸非常重要,。神經(jīng)元常常會(huì)定位在腹側(cè)腦干中,，當(dāng)血液中組分發(fā)生改變（缺少氧氣或者二氧化碳增多）時(shí)，RTN神經(jīng)元就會(huì)迅速感知并且告知機(jī)體對(duì)呼吸做出改變,。但是如果神經(jīng)元有缺失的話便會(huì)嚴(yán)重影響這一系列反應(yīng),。
在小鼠中缺失Atoh1基因?qū)?huì)給其帶來(lái)嚴(yán)重的呼吸問(wèn)題，因?yàn)樾∈蟛⒉粫?huì)自動(dòng)調(diào)節(jié)呼吸來(lái)降低血液中二氧化碳的攝入和增加氧氣的供給,。相關(guān)研究資助由美國(guó)心臟協(xié)會(huì)西南協(xié)會(huì)提供,。（生物谷Bioon.com）
編譯自：Master Gene Affects Neurons That Govern Breathing at Birth and in Adulthood
doi:10.1016/j.neuron.2012.06.027
PMC:
PMID:
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.
