Multiple knockout mouse models reveal lincRNAs are required for life and brain development

By Martin Sauvageau, L. Goff, Simona Lodato, B. Bonev, A. Groff, C. Gerhardinger, D. Sanchez-Gomez, Ezgi Hacisuleyman, Eric Li, Matthew A. Spence and 15 more. eLife, 2013

679 citations recorded by the source corpus.

Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA 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 lncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of lncRNA molecules. DOI: http://dx.doi.org/10.7554/eLife.01749.001

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/774d5e6dd2d71ed2fb4ffab3204fcb694a8f8c40

Citations in the corpus

• CRISPRi-based genome-scale identification of functional long non-coding RNA loci in human cells (2016, neutral): “Our study, which focused on lncRNAs required for robust cell growth, underestimates the true number of functional lncRNAs in these cell types, as lncRNAs have been shown to regulate more evolutionarily complex cellular decisions such as cell fate (7, 19, 57, 58), cancer metastasis (59, 60), and perh”