ICOS转基因小鼠模型的建立及其在日本血吸虫病研究中的应用

发布时间：2018-06-04 02:06

  本文选题：ICOS(Inducible + co-stimulator　； 参考：《苏州大学》2005年硕士论文

【摘要】：本课题尝试建立ICOS转基因小鼠模型,将其应用于日本血吸虫病的研究。我们采用基因工程方法克隆人的全长ICOS基因并构建转基因载体,经显微注射和胚胎移植成功建立了ICOS转基因小鼠模型,并对其生物学特性进行了初步研究,发现转基因小鼠繁殖能力和生长曲线与正常FVB小鼠(野生型)没有显著差异,脾脏、胸腺等免疫器官也无显著异常。转基因小鼠感染日本血吸虫后,检测相关的细胞因子和血清抗体,同时观察肝脏肉芽肿病变,结果表明,转基因小鼠体内免疫应答较野生型小鼠强烈,而且Th2反应更为强烈,提示共刺激分子ICOS可能在日本血吸虫特异性Th1/Th2免疫偏移及其免疫病理机制中发挥重要作用。本研究为进一步了解ICOS的免疫调节功能,深入阐明日本血吸虫病免疫致病的分子机制提供了一个潜在的模型工具,对控制虫卵肉芽肿病变,防止晚期血吸虫病的发生、发展具有重要的理论意义和应用价值。
[Abstract]:In this paper, we try to establish ICOS transgenic mice model and apply it to schistosomiasis japonica. The full-length ICOS gene of human was cloned by genetic engineering method and the transgenic vector was constructed. The ICOS transgenic mouse model was successfully established by microinjection and embryo transfer, and its biological characteristics were preliminarily studied. It was found that there was no significant difference in reproductive ability and growth curve between transgenic mice and normal FVB mice (wild type), and there was no significant abnormality in immune organs such as spleen and thymus. After the transgenic mice were infected with Schistosoma japonicum, the related cytokines and serum antibodies were detected and liver granulomatous lesions were observed. The results showed that the immune response of transgenic mice was stronger than that of wild-type mice, and the Th2 reaction was stronger in transgenic mice than in wild-type mice. The results suggest that the costimulatory molecule ICOS may play an important role in Schistosoma japonicum specific Th1/Th2 immune migration and its immunopathological mechanism. This study provides a potential model tool for further understanding the immunomodulatory function of ICOS and elucidating the molecular mechanism of immune pathogenesis of schistosomiasis japonicum, which can control egg granuloma and prevent the occurrence of advanced schistosomiasis. Development has important theoretical significance and application value.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R-332
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本文编号：1975331