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

被引：565

作者：

Sauvageau, Martin ^{[1
,2
]}

Goff, Loyal A. ^{[1
,2
,3
]}

Lodato, Simona ^{[1
,2
]}

Bonev, Boyan ^{[1
,2
]}

Groff, Abigail F. ^{[1
,2
]}

Gerhardinger, Chiara ^{[1
,2
]}

Sanchez-Gomez, Diana B. ^{[1
]}

Hacisuleyman, Ezgi ^{[1
,2
]}

Li, Eric ^{[1
]}

Spence, Matthew ^{[1
]}

Liapis, Stephen C. ^{[1
,2
]}

Mallard, William ^{[1
,2
]}

Morse, Michael ^{[1
,2
]}

Swerdel, Mavis R. ^{[4
]}

D'Ecclessis, Michael F. ^{[4
]}

Moore, Jennifer C. ^{[5
]}

Lai, Venus ^{[6
]}

Gong, Guochun ^{[6
]}

Yancopoulos, George D. ^{[6
]}

Frendewey, David ^{[6
]}

Kellis, Manolis ^{[2
,3
]}

Hart, Ronald P. ^{[4
]}

Valenzuela, David M. ^{[6
]}

Arlotta, Paola ^{[1
,2
]}

Rinn, John L. ^{[1
,2
,7
]}

机构：

[1] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA USA

[3] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA

[4] Rutgers State Univ, Dept Cell Biol & Neurosci, New Brunswick, NJ 08903 USA

[5] Rutgers State Univ, Dept Genet, New Brunswick, NJ 08903 USA

[6] Regeneron Pharmaceut Inc, VelociGene, Tarrytown, NY 10591 USA

[7] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA

来源：

ELIFE | 2013年 / 2卷

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

LONG NONCODING RNAS; RADIAL GLIA; STEM-CELLS; GENE; EXPRESSION; TRANSCRIPTION; PRECURSORS; CHROMATIN; NEURONS; MICE;

D O I：

10.7554/eLife.01749

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：24

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