Early postnatal lethality in Hoxa-5 mutant mice is attributable to respiratory tract defects
Early postnatal lethality in Hoxa-5 mutant mice is attributable to respiratory tract defects
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DOI：
10.1006/dbio.1997.8746
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发表时间：
1997-12-15
影响因子：
2.7
通讯作者：
Jeannotte, L
中科院分区：
文献类型：
--
作者：
Aubin, J;Lemieux, M;Jeannotte, L
为了揭示Hoxa-5基因在胚胎发生过程中的作用，我们重点研究了Hoxa-5纯合突变体围产期致死性器官系统的结构和功能缺陷。突变表型的分析表明，Hoxa-5是呼吸道的正常器官形成和功能所必需的。在纯合子新生儿突变体中，不适当的气管和肺形态发生可导致气管闭塞，并导致与表面活性蛋白产生显著减少相关的呼吸窘迫。总的来说，这些缺陷可能是纯合子突变幼仔明显死亡的基础。此外，Hoxa-5功能的丧失导致肺上皮中TTF-1、HNF-3 β和N-myc基因表达的改变。由于Hoxa-5的表达仅限于发育中的气管和肺的间充质组分，因此在上皮细胞中观察到的作用可能是由于正常上皮-间充质相互作用的破坏。(C)北京：科学出版社.
To uncover roles for the Hoxa-5 gene during embryogenesis, we have focused on identifying structural and functional defects in organ systems underlying the perinatal lethality in Hoxa-5 homozygous mutants. Analysis of the mutant phenotype shows that Hoxa-5 is essential for normal organogenesis and function of the respiratory tract. In homozygous newborn mutants, improper tracheal and lung morphogenesis can lead to tracheal occlusion, and to respiratory distress associated with a marked decrease in the production of surfactant proteins. Collectively, these defects likely underlie the pronounced mortality of homozygous mutant pups. Furthermore, the loss of Hoxa-5 function results in altered TTF-1, HNF-3 beta, and N-myc gene expression in the pulmonary epithelium. Since expression of Hoxa-5 is confined to the mesenchymal component of the developing trachea and lung, the effects observed in epithelial cells may result from a disruption of normal epithelial-mesenchymal interactions. (C) 1997 Academic Press.