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bioRxiv · 10.1101/2020.12.06.413633

Grb10a knockdown in Danio rerio during early life alters growth and cardiometabolic function associated with a remodelled transcriptome

Evans, B.·Garner, T.·DeLeonibus, C.·Wearing, O.·Shiels, H.·Hurlstone, A. H.·Clayton, P.·Stevens, A.
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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.

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Evans, B., Garner, T., DeLeonibus, C., Wearing, O., Shiels, H., Hurlstone, A. H., Clayton, P., Stevens, A.. 2020-12-06. Grb10a knockdown in Danio rerio during early life alters growth and cardiometabolic function associated with a remodelled transcriptome. https://doi.org/10.1101/2020.12.06.413633

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