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 G/G switch gene 2 ( G0S2) knockout (KO) chickens, and G0S2 null KO chickens showed a dramatic reduction of abdominal fat deposition without affecting other economic traits. Additionally, G0S2 null KO chickens had altered fatty acid compositions in their blood and abdominal fat compared with wild-type chickens under normal dietary conditions. The global mRNA sequencing data showed that G0S2 disruption in chickens would activate 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.-Park, T. S., Park, J., Lee, J. H., Park, J.-W., Park, B.-C. Disruption of G/G switch gene 2 ( G0S2) reduced abdominal fat deposition and altered fatty acid composition in chicken.

Current Strategies of Genomic Modification in Livestock and Applications in Poultry

“…Interestingly, these G0S2 knockout chickens did not show any phenotypic differences compared to wild-type chickens (Park et al, 2019). This G0S2 knockout line is expected to offer considerable insight into the mechanisms of fat metabolism in chickens, which could be useful for industrial applications by enabling greater control of energy balance.…”

“…The following year, Park et al (2014) reported the creation of an ovalbumin gene knockout chicken using the TALEN gene-editing platform (Park et al, 2014). More recently, there have been a handful of reports describing the generation of targeted mutants in chicken via the CRISPR/Cas9 system (Dimitrov et al, 2016;Oishi et al, 2016;Oishi et al, 2018;Park et al, 2019).…”

“…Leg weakness is commonly observed in fat broiler chickens, along with other problems, such as reduced reproductive performance in the breeding stock. Similarly, the type of fat deposited in the carcass can vary between individuals and may lead to adverse health outcomes for consumers (Park et al, 2019). To reduce fat deposition, Park et al 2019generated a G0/G1 switch gene 2 (G0S2) knockout chicken using the CRISPR/Cas9 method (Park et al, 2019).…”

“…Similarly, the type of fat deposited in the carcass can vary between individuals and may lead to adverse health outcomes for consumers (Park et al, 2019). To reduce fat deposition, Park et al 2019generated a G0/G1 switch gene 2 (G0S2) knockout chicken using the CRISPR/Cas9 method (Park et al, 2019). G0S2 was firstly identified as a key regulator in cell cycling (Siderovski et al, 1990); however, it is now known that G0S2 plays a critical role in the regulation of lipid metabolism (Yang et al, 2010;Heckmann et al, 2014;Zhang et al, 2017;Park et al, 2019 regulating the critical first step in this process by inhibiting ATGL activity (Yang et al, 2010;Heckmann et al, 2014;Zhang et al, 2017;Park et al, 2019).…”

Functional analyses of miRNA-146b-5p during myogenic proliferation and differentiation in chicken myoblasts

“…However, additional research is required because it is not clear how miR-146b-5p affects myogenic differentiation, and there are no reports addressing its effects on chicken myogenesis. Thus, in this study, we designed and constructed a miRNA expression vector system to overexpress miR-146b-5p in pCM cells using the piggyBac transposon system, which previous studies have demonstrated to be an e cient transgene delivery system [22,23]. miR-146b-5p increased proliferation and decreased differentiation by regulating genes related to the cell cycle in chicken myoblasts.…”