title: Multiple knockout mouse models reveal lincRNAs are required for life and brain development.
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(-/-) 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.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Sauvageau
authors.forename: Loyal A
authors.initials: LA
authors.lastname: Goff
authors.forename: Simona
authors.initials: S
authors.lastname: Lodato
authors.forename: Boyan
authors.initials: B
authors.lastname: Bonev
authors.forename: Abigail F
authors.initials: AF
authors.lastname: Groff
authors.forename: Chiara
authors.initials: C
authors.lastname: Gerhardinger
authors.forename: Diana B
authors.initials: DB
authors.lastname: Sanchez-Gomez
authors.forename: Ezgi
authors.initials: E
authors.lastname: Hacisuleyman
authors.forename: Eric
authors.initials: E
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Spence
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Liapis
authors.forename: William
authors.initials: W
authors.lastname: Mallard
authors.forename: Michael
authors.initials: M
authors.lastname: Morse
authors.forename: Mavis R
authors.initials: MR
authors.lastname: Swerdel
authors.forename: Michael F
authors.initials: MF
authors.lastname: D'Ecclessis
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Moore
authors.forename: Venus
authors.initials: V
authors.lastname: Lai
authors.forename: Guochun
authors.initials: G
authors.lastname: Gong
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: David
authors.initials: D
authors.lastname: Frendewey
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Hart
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Paola
authors.initials: P
authors.lastname: Arlotta
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*
chemical_list: D062085:RNA, Long Noncoding
keywords: brain development; developmental defect; knockout mouse models; lethality; long noncoding RNAs