畜牧与生物技术杂志(英文版)2024,Vol.15Issue(1) :108-126.DOI:10.1186/s40104-023-00930-4

Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

Tianqi Duo Xiaohong Liu Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang Shiyi Chen Yaosheng Chen Zuyong He
畜牧与生物技术杂志(英文版)2024,Vol.15Issue(1) :108-126.DOI:10.1186/s40104-023-00930-4

Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

Tianqi Duo 1Xiaohong Liu 1Delin Mo 1Yu Bian 2Shufang Cai 3Min Wang 1Ruiqiang Li 1Qi Zhu 1Xian Tong 1Ziyun Liang 1Weilun Jiang 1Shiyi Chen 1Yaosheng Chen 1Zuyong He1
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作者信息

  • 1. State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-Sen University,Guangzhou 510275,Guangdong,China
  • 2. Department of Pharma-cology(the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Research,Ministry of Education),College of Pharmacy,Harbin Medical University,Harbin 150081,China
  • 3. State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-Sen University,Guangzhou 510275,Guangdong,China;Hunan Provincial Key Laboratory for Genetic Improvement of Domestic Animal,College of Animal Science and Technology,Hunan Agricultural University,Changsha 410128,China
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Abstract

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2)is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymor-phism(SNP)within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thick-ness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indig-enous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce/GF2-intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs)isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT)to generate the founder line of IGF2T/T pigs.Results We found the heterozygous progeny IGF2C/T pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF)content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2C/T pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of/GF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3K-AKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2 and an example for improving porcine economic traits through precise base editing.

Key words

CBE3/IGF2/Intramuscular fat/Meat production/PI3K-AKT/AMPK/ZBED6

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基金项目

National Natural Science Foundation of China(32072697)

National Natural Science Foundation of China(32030102)

&&(CARS-PIG-35)

R&D Programmes of Guangdong Province(2018B020203003)

Laboratory of Lingnan Modern Agriculture Project(NZ2021006)

出版年

2024
畜牧与生物技术杂志(英文版)
中国科学技术协会

畜牧与生物技术杂志(英文版)

CSTPCD
影响因子:0.765
ISSN:1674-9782
参考文献量42
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