1. Transientgrb10aKnockdown Permanently Alters Growth, Cardiometabolic Phenotype and the Transcriptome inDanio rerio
- Author
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Oliver H. Wearing, Holly A. Shiels, Adam Stevens, Chiara DeLeonibus, Peter E. Clayton, Adam Hurlstone, Terence Garner, and Bridget L Evans
- Subjects
medicine.medical_specialty ,Gene knockdown ,GRB10 ,Embryogenesis ,Cardiac muscle ,Danio ,Biology ,biology.organism_classification ,Phenotype ,Transcriptome ,Metabolic pathway ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,medicine ,biology.protein - Abstract
Embryonic growth trajectory is a risk factor for chronic metabolic and cardiovascular disorder. Grb10 is a negative regulator of the main pathways driving embryonic growth. This study investigates the long-term cardiometabolic consequences and transcriptomic profiles of transient disruption of grb10a expression in Danio rerio. Knockdown was associated with increased embryonic growth (+7%) and metabolic rate (+25%), and decreased heart rate (- 50%) in early life. Juvenile growth and respiratory rate were also elevated (+30% and 7-fold increase respectively). The transcriptome was permanently remodelled by this transient disruption, with dysregulation of multiple growth, cardiac, and metabolic pathways. Phenotypic alteration persisted into adulthood, resulting in a leaner body with elevated skeletal and cardiac muscle content and aerobic scope (43%). This study not only confirms for the first time that transient disruption of a single gene can result in permanent transcriptomic remodelling but correlates this remodelling with persistent alterations to the adult cardiometabolic phenotype.
- Published
- 2020
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