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Construction of a transgenic pig model overexpressing polycystic kidney disease 2 (PKD2) gene

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic disease, affecting millions of people worldwide. The progressive growth of cysts in kidneys eventually leads to renal failure in 50 % of patients, and there is currently no effective treatment. Various murine models have been studied to elucidate the disease mechanisms, and much information has been acquired. However, the course of the disease cannot be fully recapitulated using these models. The pig is a suitable model for biomedical research, and pig PKD2 has high similarity to the human ortholog at the molecular level. Here, a mini-pig PKD2 transgenic model was generated, driven by a ubiquitous cytomegalovirus enhancer/promoter. Using somatic cell nuclear transfer, four transgenic pigs with approximately 10 insertion events each were generated. Quantitative real-time PCR and western blotting showed that PKD2 was more highly expressed in transgenic pigs than in wild-type counterparts. Because of the chronic nature of ADPKD, blood urea nitrogen and serum creatinine levels were continuously measured to assess the pig kidney function. The transgenic pigs continue to show no significant alteration in kidney function; it is estimated that 1–2 more years may be required for manifestation of renal cystogenesis in these pigs.

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Acknowledgments

This work was funded by the National Basic Research Program of China (No. 2011CB944100). We are grateful to members of the State Key Laboratory for Agrobiotechnology for helpful suggestions and discussions.

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Authors and Affiliations

  1. State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing, 100193, People’s Republic of China

    Jin He, Jianhua Ye, Zhengquan Yu, Yaofeng Zhao, Xiaoxiang Hu & Ning Li

  2. College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People’s Republic of China

    Jin He & Changxin Wu

  3. GenProtein Biotech Ltd., Beijing, 100193, People’s Republic of China

    Qiuyan Li

  4. Department of Nephrology, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China

    Yuanyuan Feng, Xueyuan Bai & Xiangmei Chen

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  1. Jin He
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  2. Jianhua Ye
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  3. Qiuyan Li
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  4. Yuanyuan Feng
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  9. Yaofeng Zhao
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  10. Xiaoxiang Hu
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  11. Ning Li
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Corresponding author

Correspondence to Ning Li.

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Jin He and Jianhua Ye contributed equally to the work.

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He, J., Ye, J., Li, Q. et al. Construction of a transgenic pig model overexpressing polycystic kidney disease 2 (PKD2) gene. Transgenic Res 22, 861–867 (2013). https://doi.org/10.1007/s11248-012-9686-z

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  • DOI: https://doi.org/10.1007/s11248-012-9686-z

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