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

文献类型： 外文期刊

第一作者： Kong, Siyuan

作者： Kong, Siyuan;Ruan, Jinxue;Xin, Leilei;Fan, Junhua;Xia, Jihan;Liu, Zhiguo;Mu, Yulian;Yang, Shulin;Li, Kui

作者机构：

关键词： multi-transgene;polycistronic system;minipigs;somatic cell nuclear transfer;diabetes

期刊名称：MOLECULAR MEDICINE REPORTS （ 影响因子：2.952； 五年影响因子：2.754 ）

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收录情况： SCI

摘要： 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-beta-hydroxysteroid dehydrogenase 1 (11 beta-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 11 beta-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 11 beta-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 beta-cell development and apoptosis. This novel tissue-specific polycistronic system offers a promising starting point for efficiently mimicking multigenic metabolic disease.

分类号： R3

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