Study of congenital central respiratory failure using mice model

为了寻找导致人类先天性呼吸衰竭的基因，我们利用野生小鼠和几个表现呼吸衰竭的基因缺陷小鼠，通过以下方法进行了研究。1)以胎鼠和新生小鼠为实验对象，采用全身体积描记技术检测呼吸参数，以评估呼吸异常。2)为阐明呼吸衰竭的发生机制，采用脑干-脊髓制备方法，对呼吸神经元进行电生理分析和光学成像分析。3)为寻找与脑干中枢性呼吸衰竭相关的基因，应用基因芯片技术检测了胚胎呼吸向外呼吸过渡过程中延髓基因表达的变化。到目前为止，我们已经对几个基因缺陷的小鼠表现出呼吸衰竭进行了研究，并提出了几种中枢性呼吸衰竭和外周呼吸衰竭的模型。例如，我们之前曾报道，Tlx3缺陷小鼠出生后24小时内死于中枢换气不足。在这里，我们证明了过度的GABA介导的抑制导致了Tlx3-/-小鼠呼吸神经网络的功能障碍。此外，同源异型盒基因Pbx3缺陷小鼠出生后24小时内死于中枢换气不足。Pbx3似乎与Tlx3相关，然而，Pbx3-/-小鼠表现出不同的呼吸障碍。此外，我们证明了DSCAM(唐氏综合征细胞黏附分子)-/-小鼠死于具有另一种呼吸模式的中枢低通气量。如上所述，我们的方法似乎在呼吸熟悉的分析中是有用的。

In order to search the genes which cause a human congenital respiratory failure, we have been studying by the following methods using wild mice and several lines of gene deficient mice that exhibit respiratory failure. 1)For the assessment of respiratory abnormality, ventilatory parameters were checked out by whole body plethysmography using prenatal and neonatal mice. 2)To clarify the mechanism of the respiratory failure, the respiratory neuron activity was examined by electrophysiological analysis and optical imaging analysis using the brainstem-spinal cord preparation. 3)To search for the genes that relate the central respiratory failure in brainstem, the alteration of gene expression in the medulla oblongata during transition from embryonic respiration to external respiration was examined by DNA microarray. Until now, we have studied several lines of gene deficient mice exhibit respiratory failure and proposed the several models of central respiratory failure and peripheral respiratory failure. For example, we previously reported that Tlx3 deficient mice die within 24hrs after birth from a central hypoventilation. Here, we demonstrated that the excess GABA-mediated inhibition caused dysfunction of respiratory neuronal network on Tlx3-/- mice. Also homeobox gene Pbx3 deficient mice die within 24hrs after birth from a central hypoventilation. Pbx3 seems to be correlated with Tlx3, however, Pbx3-/- mice showed a different respiratory disorder. Furthermore, we demonstrated that DSCAM (Down syndrome cell adhesion molecule) -/- mice die from a central hypoventilation with another respiratory pattern. As observed above, our approach seems to be useful in analysis of respiratory familiar.