A genetic model for a central (septum transversum) congenital diaphragmatic hernia in mice lacking Slit3
A genetic model for a central (septum transversum) congenital diaphragmatic hernia in mice lacking Slit3
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DOI：
10.1073/pnas.0730709100
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发表时间：
2003-04-29
影响因子：
11.1
通讯作者：
Ornitz, DM
中科院分区：
文献类型：
--
作者：
Yuan, WL;Rao, Y;Ornitz, DM
先天性膈疝（CDH）是人类儿童死亡率的重要原因，其病因异质性和知之甚少。在这里，我们发现缺乏Slit3的小鼠发生了中央（横隔）CDH。SUB编码引导分子Slit家族的一个成员，在胚胎发育期间主要在膈膜间皮中表达。在SUB - null小鼠中，由于形态发生异常，膈肌中央肌腱区无法与肝组织分离。CDH通过肝脏的持续生长发展到胸腔。本研究建立了CDH的第一个遗传模型，并确定了Slit3在调节膈肌发育中的作用。
Congenital diaphragmatic hernia (CDH) is a significant cause of pediatric mortality in humans with a heterogeneous and poorly understood etiology. Here we show that mice lacking Slit3 developed a central (septum transversum) CDH. SUB encodes a member of the Slit family of guidance molecules and is expressed predominantly in the mesothelium of the diaphragm during embryonic development. In SUB null mice, the central tendon region of the diaphragm fails to separate from liver tissue because of abnormalities in morphogenesis. The CDH progresses through continuous growth of the liver into the thoracic cavity. This study establishes the first genetic model for CDH and identifies a previously unsuspected role for Slit3 in regulating the development of the diaphragm.