Journal
ELIFE
Volume 2, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.01749
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Funding
- National Institutes of Health [DP2OD006670, P01 GM099117, NS062489, NS073124, NS078164]
- Center for Cell Circuits [P50 HG006193-01]
- New York Stem Cell Foundation
- Harvard Stem cell Institute
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0644282] Funding Source: National Science Foundation
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Many studies are uncovering functional roles for long noncoding RNAs (IncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of IncRNAs in various physiological conditions, we have developed a collection of 18 IncRNA knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc-Brn1b and linc-Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr(-/-) neonates, whereas linc-Brn1b(-/-) mutants displayed distinct abnormalities in the generation of upper layer II-IV neurons in the neocortex. This study demonstrates that IncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of IncRNA molecules.
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