Lai Ka-Man Venus, Gong Guochun, Atanasio Amanda, Rojas José, Quispe Joseph, Posca Julita, White Derek, Huang Mei, Fedorova Daria, Grant Craig, Miloscio Lawrence, Droguett Gustavo, Poueymirou William T, Auerbach Wojtek, Yancopoulos George D, Frendewey David, Rinn John, Valenzuela David M
VelociGene, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States of America.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, United States of America; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
PLoS One. 2015 Apr 24;10(4):e0125522. doi: 10.1371/journal.pone.0125522. eCollection 2015.
In a survey of 20 knockout mouse lines designed to examine the biological functions of large intergenic non-coding RNAs (lincRNAs), we have found a variety of phenotypes, ranging from perinatal lethality to defects associated with premature aging and morphological and functional abnormalities in the lungs, skeleton, and muscle. Each mutant allele carried a lacZ reporter whose expression profile highlighted a wide spectrum of spatiotemporal and tissue-specific transcription patterns in embryos and adults that informed our phenotypic analyses and will serve as a guide for future investigations of these genes. Our study shows that lincRNAs are a new class of encoded molecules that, like proteins, serve essential and important functional roles in embryonic development, physiology, and homeostasis of a broad array of tissues and organs in mammals.
在一项针对20种基因敲除小鼠品系的调查中,旨在研究大型基因间非编码RNA(lincRNA)的生物学功能,我们发现了各种各样的表型,从围产期致死到与早衰相关的缺陷以及肺、骨骼和肌肉的形态和功能异常。每个突变等位基因都携带一个lacZ报告基因,其表达谱突出了胚胎和成年期广泛的时空和组织特异性转录模式,为我们的表型分析提供了信息,并将作为未来这些基因研究的指南。我们的研究表明,lincRNA是一类新的编码分子,与蛋白质一样,在哺乳动物多种组织和器官的胚胎发育、生理学和体内平衡中发挥着至关重要的功能作用。