TY - JOUR TI - Multiple knockout mouse models reveal lincRNAs are required for life and brain development AU - Sauvageau, Martin AU - Goff, Loyal A AU - Lodato, Simona AU - Bonev, Boyan AU - Groff, Abigail F AU - Gerhardinger, Chiara AU - Sanchez-Gomez, Diana B AU - Hacisuleyman, Ezgi AU - Li, Eric AU - Spence, Matthew AU - Liapis, Stephen C AU - Mallard, William AU - Morse, Michael AU - Swerdel, Mavis R AU - D’Ecclessis, Michael F AU - Moore, Jennifer C AU - Lai, Venus AU - Gong, Guochun AU - Yancopoulos, George D AU - Frendewey, David AU - Kellis, Manolis AU - Hart, Ronald P AU - Valenzuela, David M AU - Arlotta, Paola AU - Rinn, John L A2 - Reinberg, Danny VL - 2 PY - 2013 DA - 2013/12/31 SP - e01749 C1 - eLife 2013;2:e01749 DO - 10.7554/eLife.01749 UR - https://doi.org/10.7554/eLife.01749 AB - 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. KW - long noncoding RNA KW - knockout mouse model KW - lethality KW - developmental defect KW - brain development JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -