Disruption of G0/G1 switch gene 2 (G0S2) reduced abdominal fat deposition and altered fatty acid composition in chicken

Abstract

Chicken as a food source is one of the most widespread domestic animals, and it has been used extensively as a research model. The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system is the most efficient and reliable tool for precise genome-targeted modification and has generated considerable excitement for industrial applications, as well as biologic science. Unlike in mammals, germline-transmittable primordial germ cells (PGCs) in chicken were used as an alternative strategy for the production of genetically altered chickens. Here, by combining the CRISPR-Cas9 platform and germ cell-mediated germline transmission, we generated G0/G1 switch gene 2 (G0S2) knockout (KO) chickens, andG0S2nullKO chickens showed a dramatic reduction of abdominal fat deposition without affecting other economic traits. Additionally, G0S2 null KO chickenshad altered fatty acid compositionsintheirblood and abdominalfat comparedwithwild-type chickensunder normaldietary conditions.TheglobalmRNA sequencingdata showedthatG0S2disruptionin chickenswouldactivate the adipose tissue-specific peroxisomal oxidation pathway, and enoyl-coenzyme A (CoA), hydratase/3-hydroxyacyl CoA dehydrogenase might be a target molecule in metabolic homeostasis in the chicken adipose tissue. Our results demonstrate that the CRISPR-Cas9 system with chicken PGCs can facilitate the production of specific genome-edited chickens for practical applications, as well as basic research.