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种表现出呼吸衰竭的基因缺陷小鼠进行了以下方法的研究。1)为评估呼吸异常，采用产前和新生小鼠全身体积脉搏图检查通气参数。2)为明确呼吸衰竭的发生机制，采用脑干-脊髓制备，通过电生理分析和光学成像分析检测呼吸神经元活动。3)为了寻找脑干中枢呼吸衰竭的相关基因，采用DNA芯片检测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，我们已经研究了几种表现出呼吸衰竭的基因缺陷小鼠，并提出了中枢性呼吸衰竭和外周性呼吸衰竭的几种模型。例如，我们之前报道过Tlx3缺陷小鼠在出生后24小时内死于中枢性低通气。在这里，我们证明了过量的gaba介导的抑制导致Tlx3-/-小鼠呼吸神经网络功能障碍。此外，同源盒基因Pbx3缺陷小鼠在出生后24小时内死于中枢性低通气。Pbx3似乎与Tlx3相关，然而，Pbx3-/-小鼠表现出不同的呼吸系统疾病。此外，我们证明了DSCAM（唐氏综合征细胞粘附分子）-/-小鼠死于另一种呼吸模式的中央低通气。正如上面所观察到的，我们的方法在分析呼吸熟悉物时似乎是有用的。

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.