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
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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