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Publication
Alteration of NCoR corepressor splicing in mice causes increased body weight and
hepatosteatosis without glucose intolerance.
Authors Goodson ML, Young BM, Snyder CA, Schroeder AC, Privalsky ML
Submitted By Martin Privalsky on 4/9/2015
Status Published
Journal Molecular and cellular biology
Year 2014
Date Published
Volume : Pages 34 : 4104 - 4114
PubMed Reference 25182530
Abstract Alternative mRNA splicing is an important means of diversifying function in
higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to
alternative mRNA splicing, yielding a series of distinct corepressor variants
with highly divergent functions. Normal adipogenesis is associated with a switch
in corepressor splicing from NCoR? to NCoRd, which appears to help regulate this
differentiation process. We report here that mimicking this development switch
in mice by a splice-specific whole-animal ablation of NCoR? is very different
from a whole-animal or tissue-specific total NCoR knockout and produces
significantly enhanced weight gain on a high-fat diet. Surprisingly, NCoR?(-/-)
mice are protected against diet-induced glucose intolerance despite enhanced
adiposity and the presence of multiple additional, prodiabetic phenotypic
changes. Our results indicate that the change in NCoR splicing during normal
development both helps drive normal adipocyte differentiation and plays a key
role in determining a metabolically appropriate storage of excess calories. We
also conclude that whole-gene "knockouts" fail to reveal how important gene
products are customized, tailored, and adapted through alternative mRNA splicing
and thus do not reveal all the functions of the protein products of that gene.




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