Multiple knockout mouse models reveal lincRNAs are required for life and brain development
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Kellis_Multiple knockout.pdf
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Author(s)
Goff, Loyal
Kellis, Manolis
Sauvageau, Martin
Lodato, Simona
Bonev, Boyan
Groff, Abigail F.
Gerhardinger, Chiara
Sanchez-Gomez, Diana B.
Hacisuleyman, Ezgi
Li, Eric
Date Issued
December 2013
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Sauvageau, M., L. A. Goff, S. Lodato, B. Bonev, A. F. Groff, C. Gerhardinger, D. B. Sanchez-Gomez, et al. “Multiple Knockout Mouse Models Reveal lincRNAs Are Required for Life and Brain Development.” eLife 2, no. 0 (December 31, 2013): e01749–e01749.
Version
Final published version
Abstract
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[superscript −/−] neonates, whereas linc–Brn1b[superscript −/−] 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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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DOI of Published Version
https://doi.org/10.7554/eLife.01749
