Mutation of mouse Samd4 causes leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling
Abstract
Whereas many heritable obesity phenotypes are known, lean phenotypes are comparatively uncommon. Yet they can reveal critical checkpoints regulating energy balance. During a large-scale random germ-line mutagenesis project, we identified mice with a lean phenotype, myopathy, excessive energy expenditure despite diminished cage activity, and impaired glucose tolerance. This phenotype, termed "supermodel," was strictly recessive and was ascribed to a missense mutation in Sterile alpha motif domain containing protein 4 (Samd4), a gene encoding an RNA-binding protein with no previously known function in mammals. This study provides evidence that Samd4 modulates the activities of the mechanistic target of rapamycin complex 1, a master regulator of metabolism.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- May 2014
- DOI:
- 10.1073/pnas.1406511111
- Bibcode:
- 2014PNAS..111.7367C