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Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs

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Abstract

Insulin-like growth factor 2 (IGF2) is an important growth factor, which promotes growth and development in mammals during fetal and postnatal stages. Using CRISPR–Cas9 system, we generated multiple founder pigs containing 12 different mutant alleles around a regulatory element within the intron 3 of IGF2 gene. Crossing two male founders passed four mutant alleles onto F1 generation, and these mutations abolished repressor ZBED6 binding and rendered this regulatory element nonfunctional. Both founders and F1 animals showed significantly faster growth, without affecting meat quality. These results indicated that editing IGF2 intron 3–3072 site using CRISPR–Cas9 technology improved meat production in Bama pigs. This is the first demonstration that editing non-coding region can improve economic traits in livestock.

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Abbreviations

Cas9:

CRISPR-associated protein 9

CRISPR:

Clustered, regularly interspaced, short-palindromic repeats

EMSA:

Electrophoretic mobility shift assay

GM:

Genetically modified

IGF2:

Insulin-like growth factor 2

QTL:

Trait locus

QTN:

Quantitative trait nucleotide

sgRNA:

Single-guide RNA

WT:

Wild type

ZBED6:

BED-type containing 6

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Acknowledgements

We thank H.W and Q.Z laboratory members for helpful discussions and comments on the manuscript. H.W was supported by Strategic Priority Research Program of Chinese Academy of Sciences (no. XDA16010205), the National Natural Science Foundation of China (nos. 31471215 and 31722036), and National Key Research and Development Program of China (no. 2016YFA0101402). Q.Z was supported by National Natural Science Foundation of China Grants 31422038, 31471395, and 31501188; National High Technology Research and Development Program Grants 2015AA020307 and 2014BAI02B01; National Basic Research Program of China Grants 2014CB964900 and 2014CB964800; National Special Key Project for Transgenic Breeding 2016ZX08010001.

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Author notes

  1. Guanghai Xiang, Jilong Ren, and Tang Hai have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China

    Guanghai Xiang, Jilong Ren, Tang Hai, Rui Fu, Dawei Yu, Jing Wang, Wei Li, Haoyi Wang & Qi Zhou

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Guanghai Xiang, Jilong Ren, Wei Li, Haoyi Wang & Qi Zhou

  3. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China

    Tang Hai, Wei Li, Haoyi Wang & Qi Zhou

  4. College of Life Sciences, Qufu Normal university, Qufu, 273165, China

    Jing Wang

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  1. Guanghai Xiang
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  2. Jilong Ren
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  4. Rui Fu
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  7. Wei Li
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Correspondence to Haoyi Wang or Qi Zhou.

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Conflict of interest

Guanghai Xiang, Jilong Ren, Tang Hai, Rui Fu, Dawei Yu, Jing Wang, Wei Li, Haoyi Wang, and Qi Zhou declare that they have no conflict of interest.

Ethical approval

All experiments related to animal work described in this study were performed strictly in accordance with the guidelines for the Care and Use of Laboratory Animals, and approved by Animal Welfare and Research Ethics Committee of Institute of Zoology, Chinese Academy of Sciences (Animal Ethics Investigation AEI-12-04-2014). All surgical procedures were performed under anesthesia, and great efforts were made to minimize animal suffering.

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Xiang, G., Ren, J., Hai, T. et al. Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs. Cell. Mol. Life Sci. 75, 4619–4628 (2018). https://doi.org/10.1007/s00018-018-2917-6

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  • DOI: https://doi.org/10.1007/s00018-018-2917-6

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