Caron K M, Smithies O
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):615-9. doi: 10.1073/pnas.98.2.615. Epub 2001 Jan 9.
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.
肾上腺髓质素是一种最近发现的强效血管舒张剂，广泛表达，并且被认为具有从生殖到血压调节等多种功能。为了阐明这些功能并更精确地确定肾上腺髓质素（Adm）的表达位点，我们用编码增强型绿色荧光蛋白的序列替换了小鼠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缺失可能是人类非免疫性胎儿水肿的一个原因。
