Multiple knockout mouse models reveal lincRNAs are required for life and brain development
0301 basic medicine
570
Mouse
QH301-705.5
Science
610
brain development
lethality
Mice
03 medical and health sciences
knockout mouse models
Animals
long noncoding RNAs
long noncoding RNA
Biology (General)
Mice, Knockout
0303 health sciences
Q
R
Brain
knockout mouse model
3. Good health
Developmental Biology and Stem Cells
Medicine
RNA, Long Noncoding
developmental defect
DOI:
10.7554/elife.01749
Publication Date:
2013-11-26T14:29:10Z
AUTHORS (25)
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.
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