Open Access

Multi‑transgenic minipig models exhibiting potential for hepatic insulin resistance and pancreatic apoptosis

  • Authors:
    • Siyuan Kong
    • Jinxue Ruan
    • Leilei Xin
    • Junhua Fan
    • Jihan Xia
    • Zhiguo Liu
    • Yulian Mu
    • Shulin Yang
    • Kui Li
  • View Affiliations

  • Published online on: November 19, 2015     https://doi.org/10.3892/mmr.2015.4582
  • Pages: 669-680
  • Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

There are currently no multi‑transgenic minipig models of diabetes for the regulation of multiple genes involved in its pathogenesis. The foot and mouth disease virus 2A (F2A)‑mediated polycistronic system possesses several advantages, and the present study developed a novel multi‑transgenic minipig model associated with diabetes using this system. The tissue‑specific polycistronic system used in the present study consisted of two expression cassettes, separated by an insulator: (i) 11‑β‑hydroxysteroid dehydrogenase 1 (11β‑HSD1), driven by the porcine liver‑specific apolipoprotein E promoter; (ii) human islet amyloid polypeptide (hIAPP) and C/EBP homologous protein (CHOP), linked to the furin digested site and F‑2A, driven by the porcine pancreas‑specific insulin promoter. In the present study, porcine fetal fibroblasts were transfected with this vector. Following somatic cell nuclear transfer using 10 cell clones and the transplantation of 1,459 embryos in total, three Landrace x Yorkshire surrogates became pregnant and delivered three Wuzhishan piglets. Genomic polymerase chain reaction (PCR) demonstrated that the piglets were multi‑transgenic. Reverse transcription‑quantitative PCR confirmed that 11β‑HSD1 transcription was upregulated in the targeted liver. Similarly, hIAPP and CHOP were expressed at high levels, compared with the control (P<0.05 and P<0.01) in the pancreas, consistent with the western blotting and immunohistochemistry results. The primary results also showed that overexpression of 11β‑HSD1 in the liver increased the liver fat lipid parameters; and the levels of hIAPP and CHOP in the pancreatic islet cells, leading to delayed β‑cell development and apoptosis. This novel tissue‑specific polycistronic system offers a promising starting point for efficiently mimicking multigenic metabolic disease.
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January-2016
Volume 13 Issue 1

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Spandidos Publications style
Kong S, Ruan J, Xin L, Fan J, Xia J, Liu Z, Mu Y, Yang S and Li K: Multi‑transgenic minipig models exhibiting potential for hepatic insulin resistance and pancreatic apoptosis. Mol Med Rep 13: 669-680, 2016
APA
Kong, S., Ruan, J., Xin, L., Fan, J., Xia, J., Liu, Z. ... Li, K. (2016). Multi‑transgenic minipig models exhibiting potential for hepatic insulin resistance and pancreatic apoptosis. Molecular Medicine Reports, 13, 669-680. https://doi.org/10.3892/mmr.2015.4582
MLA
Kong, S., Ruan, J., Xin, L., Fan, J., Xia, J., Liu, Z., Mu, Y., Yang, S., Li, K."Multi‑transgenic minipig models exhibiting potential for hepatic insulin resistance and pancreatic apoptosis". Molecular Medicine Reports 13.1 (2016): 669-680.
Chicago
Kong, S., Ruan, J., Xin, L., Fan, J., Xia, J., Liu, Z., Mu, Y., Yang, S., Li, K."Multi‑transgenic minipig models exhibiting potential for hepatic insulin resistance and pancreatic apoptosis". Molecular Medicine Reports 13, no. 1 (2016): 669-680. https://doi.org/10.3892/mmr.2015.4582