Dominant-negative mutant hepatocyte nuclear factor 1α induces diabetes in transgenic-cloned pigs
Dominant-negative mutant hepatocyte nuclear factor 1α induces diabetes in transgenic-cloned pigs
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DOI：
10.1007/s11248-009-9262-3
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发表时间：
2009-10-01
影响因子：
3
通讯作者：
Nagashima, Hiroshi
中科院分区：
文献类型：
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作者：
Umeyama, Kazuhiro;Watanabe, Masahito;Nagashima, Hiroshi
猪已被公认为是研究各种人类健康问题的优秀生物医学模型。我们开发了表现出明显糖尿病症状的转基因猪。利用胞浆内精子注射介导的基因转移和体细胞核移植相结合的技术，获得了携带突变的人肝细胞核因子1α基因的转基因克隆猪，该基因可导致年轻人的3型成熟型糖尿病。虽然获得的22个克隆后代中的大多数在断奶前死亡，但有4头存活20-196天的猪被诊断为非空腹血糖水平超过200 mg/dl的糖尿病。一只克隆猪的口服葡萄糖耐量试验也显示，葡萄糖负荷后血糖水平显著升高。克隆猪胰腺组织的组织化学分析显示，小而不规则的朗格汉斯胰岛，胰岛素分泌不足。
Pigs have been recognized as an excellent biomedical model for investigating a variety of human health issues. We developed genetically modified pigs that exhibit the apparent symptoms of diabetes. Transgenic cloned pigs carrying a mutant human hepatocyte nuclear factor 1 alpha gene, which is known to cause the type 3 form of maturity-onset diabetes of the young, were produced using a combined technology of intracytoplasmic sperm injection-mediated gene transfer and somatic cell nuclear transfer. Although most of the 22 cloned offspring obtained died before weaning, four pigs that lived for 20-196 days were diagnosed as diabetes mellitus with nonfasting blood glucose levels greater than 200 mg/dl. Oral glucose tolerance test on a cloned pig also revealed a significant increase of blood glucose level after glucose loading. Histochemical analysis of pancreas tissue from the cloned pigs showed small and irregularly formed Langerhans Islets, in which poor insulin secretion was detected.