摘要糖尿病是一种以高血糖为特征的代谢性疾病。高血糖则是由于胰岛素分泌缺陷或其生物作用受损，或两者兼有引起。糖尿病时长期存在的高血糖，导致各种组织，特别是眼、肾、心脏、血管、神经的慢性损害、功能障碍。糖尿病已成为全人类继恶性肿瘤和心脑血管病之后的严重威胁人类健康的第三大非传染性疾病。目前我国已成世界第一糖尿病大国。由于糖尿病属于并非单一病因所引起的单一疾病，并且无法根治。为探清糖尿病病因,建立理想的动物模型是十分必要的。51710

胰岛因子1（Islet1，Isl1）是一种多效转录因子，在不同的时间、不同的组织细胞中作用于多种下游靶基因，产生不同的调控作用。在胚胎时期，Isl1通过影响细胞的增殖、分化火迁移功能，对运动神经元的分化、心肌的发育以及胰岛素的形成发挥重要作用。在出生后，Isl1在神经系统、胰岛组织中继续发挥维持细胞表型的作用，而其表达异常与糖尿病或神经系统疾病相关。此外在消化道、生殖细胞、肾脏、肺、胰腺以及神经系统的肿瘤组织中也检测到Isl1的异常表达。由于Isl1基因具有高度的种属保守性，在人、大鼠和仓鼠中，其编码的氨基酸序列完全一致。构建小鼠模型一般都采用Cre-LoxP重组酶系统的转基因小鼠作为模型，本课题采用Cre-LoxP系统构建的Isl1-Cre小鼠，为相关研究提供LoxP位点的Flox小鼠。将构建完成的Isl1CreER小鼠做详细的基因型分析，为后续研究提供有价值的材料。

Abstract Diabetes is a metabolic disease characterized by high blood sugar. Hyperglycemia is damaged due to insulin secretion defect or its biological function, or both. Diabetes chronic high blood sugar, leading to various tissues, especially the eyes, kidneys, heart, blood vessels, nerve of chronic damage, dysfunction. Diabetes has become all mankind after malignant tumor and cardio-cerebrovascular diseases of a serious threat to human health's third largest non-communicable diseases. At present our country has become the world's first diabetes superpower. Because diabetes belongs to is not a single disease caused by a single cause, and cannot effect a radical cure. In order to establish the ideal out diabetes causes, animal models is very necessary.

Islet factor 1 (Islet1, Isl1) is a kind of multiple effect of transcription factors, in different time, different role in tissue cells in a variety of downstream target genes, produce different regulation function. In embryonic period, Isl1 by influencing the cell migration, proliferation and differentiation, fire for the development of motor neuron differentiation, myocardial and play an important role in the formation of insulin. After birth, Isl1 in nervous system, pancreas tissues continue to play a role of maintain the cell phenotype, and the abnormal expression is associated with diabetes or neurological disease. In addition in the digestive tract, reproductive cells, kidney, lung, pancreas, and nervous system also detect Isl1 abnormal expression in tumor tissues. Because the Isl1 gene has a high degree of species conservative, in people, rats and hamsters, the coding sequence of amino acids. Building mouse model is generally the Cre - LoxP recombination enzyme system of genetically modified mice as a model, this topic Cre - LoxP system was used to construct the Isl1 - Cre mice, providing LoxP loci Flox mice for related research. Will build a complete model of diabetes mice do detailed analysis of the genotypes, provide valuable materials for further research.

毕业论文关键词：Isl1条件性敲除转基因小鼠； 糖尿病； PCR扩增； 

Keywords：Isl1 conditional knockout transgenic mice；Diabetes；Amplifled by PCR technology

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Abstract