A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry.

A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry.
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DOI:
10.1371/journal.pone.0132475
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Onimaru H
Onimaru H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ikeda K;Takahashi M;Sato S;Igarashi H;Ishizuka T;Yawo H;Arata S;Southard-Smith EM;Kawakami K;Onimaru H

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呼吸神经中枢的关键作用是产生呼吸节律,通过控制动脉血pCO 2/pH和pO 2水平维持体内平衡。负责新生大鼠呼吸节律产生的神经元网络位于延髓腹侧,由两组组成:面旁呼吸组(pFRG)和前Bötinger复合体组(preBötC)。pFRG在后斜方核(RTN)中部分重叠,这最初在成年猫和大鼠中发现。RTN/pFRG中的部分吸气前(Pre-I)神经元作为中枢化学感受器神经元,CO2敏感的Pre-I神经元表达同源框基因Phox 2b。Phox 2b编码一种转录因子,对感觉运动内脏回路的发育至关重要。人PHOX 2B的突变导致先天性低通气综合征,其特征在于对高碳酸血症的缓解反应迟钝。在这里,我们描述了一种新的转基因(Tg)大鼠窝藏荧光标记的前-I神经元的RTN/pFRG的一代。此外,Tg大鼠在自主肠神经元和颈动脉体中显示荧光信号。由于Tg大鼠在发育过程中在PHOX 2B阳性细胞中表达诱导型Cre重组酶,因此它是一种潜在的强大工具,可用于解剖发育过程中呼吸神经网络的全貌,并用于识别成人中枢和外周神经系统中的CO2/O2传感器分子。
The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2 levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG) and the pre-Bötzinger complex group (preBötC). The pFRG partially overlaps in the retrotrapezoid nucleus (RTN), which was originally identified in adult cats and rats. Part of the pre-inspiratory (Pre-I) neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2 sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg) rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2 sensor molecules in the adult central and peripheral nervous systems.
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