Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene.
Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene.
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DOI：
10.1073/pnas.98.2.615
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发表时间：
2001-01
影响因子：
11.1
通讯作者：
K. Caron;O. Smithies
中科院分区：
文献类型：
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作者：
K. Caron;O. Smithies
肾上腺髓质素是近年来发现的一种强有力的血管扩张剂，广泛表达，并被认为具有从生殖到血压调节的功能。为了阐明这些功能和更精确地定义Adm表达的位点，我们用编码增强型绿色荧光蛋白的序列替换了小鼠中Adm基因的编码区，同时保持Adm启动子完整。我们发现Adm（-/-）胚胎在妊娠中期死亡，伴有严重的胎儿水肿和心血管异常，包括心室小梁过度发育和动脉壁发育不全。这些数据表明，基因决定的Adm的缺乏可能是人类非免疫性胎儿水肿的原因之一。
Adrenomedullin, a recently identified potent vasodilator, is expressed widely and has been suggested to have functions ranging from reproduction to blood pressure regulation. To elucidate these functions and define more precisely sites of Adm expression, we replaced the coding region of the Adm gene in mice with a sequence encoding enhanced green fluorescent protein while leaving the Adm promoter intact. We find that Adm(-/-) embryos die at midgestation with extreme hydrops fetalis and cardiovascular abnormalities, including overdeveloped ventricular trabeculae and underdeveloped arterial walls. These data suggest that genetically determined absence of Adm may be one cause of nonimmune hydrops fetalis in humans.