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Validation of a Mouse Model to Disrupt LINC Complexes in a Cell-specific Manner
Published on: December 10, 2015
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Multiple knockout mouse models reveal lincRNAs are required for life and brain development
Martin Sauvageau1, Loyal A Goff, Simona Lodato
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.
Elife
|January 2, 2014
Summary
Researchers created 18 long noncoding RNA (lncRNA) knockout mouse strains to study their in vivo roles. Several strains showed severe developmental defects, proving lncRNAs are critical for physiological functions.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their functional roles.
- However, their in vivo relevance is often unconfirmed due to a lack of animal models.
Purpose of the Study:
- To investigate the in vivo functional relevance of lncRNAs.
- To create and characterize a collection of lncRNA knockout mouse strains.
Main Methods:
- Development of 18 lncRNA knockout mouse strains, maintaining locus transcriptional activity.
- Phenotypic characterization of knockout strains, including peri- and postnatal viability, growth, and specific organ system analysis.
Main Results:
- Three strains (Fendrr, Peril, Mdgt) exhibited peri- and postnatal lethality, with Peril and Mdgt showing incomplete penetrance and growth defects.
- Two additional strains (linc-Brn1b, linc-Pint) displayed growth defects.
- Fendrr knockout mutants showed defects in lung, gastrointestinal tract, and heart development.
- linc-Brn1b knockout mutants exhibited abnormalities in neocortical neuron generation.
Conclusions:
- lncRNAs play critical roles in vivo.
- This study provides a valuable resource and framework for future large-scale functional investigations of lncRNAs.
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