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

• DOI: 10.7554/elife.01749
• Publication Date: 2013-11-26T14:29:10Z
• Authors: Martin Sauvageau; Loyal A Goff; Simona Lodato; Boyan Bonev; Abigail F Groff; Chiara Gerhardinger; Diana B Sanchez-G...; Ezgi Hacisuleyman; Eric Li; Matthew Spence; Stephen C Liapis; William Mallard; Michael Morse; Mavis R Swerdel; Michael F D’Eccle...; Jennifer C Moore; Venus Lai; Guochun Gong; George D Yancopoulos; David Frendewey; Manolis Kellis; Ronald P Hart; David M Valenzuela; Paola Arlotta; John L Rinn
• Keywords: Penetrance; Knockout mouse; Neocortex

Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested in vivo relevance through genetic ablation animal models. To investigate the of lncRNAs various physiological conditions, we developed a collection 18 lncRNA knockout strains which locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes three mutant (Fendrr, Peril, Mdgt), latter two exhibiting incomplete penetrance growth defects survivors. We also report additional (linc-Brn1b linc-Pint). Further analysis lung, gastrointestinal tract, heart Fendrr(-/-) neonates, whereas linc-Brn1b(-/-) mutants displayed distinct abnormalities generation upper layer II-IV neurons neocortex. This study demonstrates that play critical provides framework impetus future larger-scale investigation into molecules. DOI: http://dx.doi.org/10.7554/eLife.01749.001.