Disruption of Pik3r1 Promotes Muscle Hyperplasia and Lipolysis in Grass Carp (Ctenopharyngodon idella)

Grass carp (Ctenopharyngodon idella) is a major aquaculture species, yet production efficiency is often constrained by growth performance and metabolic disorders such as hepatic lipid deposition. Traditional breeding has reached a bottleneck, necessitating precision genetic interventions. In this study, we combined comparative transcriptomics with CRISPR/Cas9- mediated gene disruption to investigate the regulatory role of Pik3r1. Comparative RNA-seq of fast- and slow-growing individuals identified Pik3r1 as a candidate gene showing an inverse association with body weight trait. To validate its function, we generated mosaic Pik3r1 knockout (KO) fish by targeting the SH3 domain of Pik3r1. The disruption of Pik3r1 conferred a profound growth advantage, increasing body weight by 82.1% and body length by 17.9% compared to wild-type controls. Histological analyses revealed that enhanced muscle accretion was driven by both hypertrophy with a 22.50% increase in myofiber cross-sectional area and hyperplasia characterized by a 18.90% rise in fiber density, coupled with a 67.7% reduction in hepatic lipid accumulation. At the molecular level, Pik3r1 disruption attenuated its inhibitory effect on the PI3K/AKT/mTOR cascade, together with upregulation of PPARα. Collectively, our results support Pik3r1 as a key regulator linking somatic growth and lipid metabolism in grass carp, and highlight its potential as a target for molecular breeding aimed at improving yield and carcass quality.