MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth
MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth
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DOI：
10.1038/nn1129
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发表时间：
2003-10-01
影响因子：
25
通讯作者：
Sieweke, MH
中科院分区：
文献类型：
--
作者：
Blanchi, B;Kelly, LM;Sieweke, MH
产生呼吸节律的脑干神经元发育的遗传基础尚不清楚。在这里，我们表明，小鼠缺乏转录因子MafB死于中枢性呼吸暂停在出生时，是有缺陷的呼吸节律在体外。MafB在preBotzinger复合体（preBotC）中的神经元亚群中表达，preBotC是假定的节律发生的主要位点。Mafb（-/-）小鼠的脑干对preBotC电解损伤或刺激以及通过缺氧或肽能输入调节节律不敏感。此外，在Mafb（-/-）小鼠中，preBotC，而不是主要的神经调节组，表现出严重的解剖缺陷，细胞结构丧失。我们的研究结果表明MafB在中枢呼吸控制中的重要作用，可能涉及到节律性preBotC神经元的规范。
The genetic basis for the development of brainstem neurons that generate respiratory rhythm is unknown. Here we show that mice deficient for the transcription factor MafB die from central apnea at birth and are defective for respiratory rhythmogenesis in vitro. MafB is expressed in a subpopulation of neurons in the preBotzinger complex (preBotC), a putative principal site of rhythmogenesis. Brainstems from Mafb(-/-) mice are insensitive to preBotC electrolytic lesion or stimulation and modulation of rhythmogenesis by hypoxia or peptidergic input. Furthermore, in Mafb(-/-) mice the preBotC, but not major neuromodulatory groups, presents severe anatomical defects with loss of cellularity. Our results show an essential role of MafB in central respiratory control, possibly involving the specification of rhythmogenic preBotC neurons.