Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alleles
-
Animals
-
Embryonic Development / genetics
-
Female
-
Genes, Reporter / genetics
-
Male
-
Mammals / genetics
-
Membrane Transport Proteins / genetics
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Phenotype
-
RNA, Long Noncoding / genetics*
-
Transcription, Genetic / genetics*
-
Transcriptome / genetics*
Substances
-
Membrane Transport Proteins
-
RNA, Long Noncoding
-
lactose permease
Grants and funding
Regeneron Pharmaceuticals, Inc., provided support in the form of salaries for the authors; Ka-Man Venus Lai, Guochun Gong, Amanda Atanasio, José Rojas, Joseph Quispe, Julita Posca, Derek White, Mei Huang, Daria Fedorova, Craig Grant, Lawrence Miloscio, Gustavo Droguett, William T. Poueymirou, Wojtek Auerbach, George D. Yancopoulos, David Frendewey and David M. Valenzuela, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.