IN VIVO ANALYSIS OF INTRACELLULAR SIGNALS CONTROLLING LYMPHOCYTE

细胞内信号传导在淋巴细胞发育中起着至关重要的作用 和功能 一组参与信号传导的分子已经被 并记录了这些分子之间的化学相互作用。 然而，它仍然在很大程度上难以捉摸，是否以及如何激活 单个信号分子的表达有助于各种体内 抗原受体基因控制等生理现象 重排，库选择，耐受诱导，外周 淋巴细胞活化和免疫记忆的维持。 由于这些 这些问题只能在体内系统中适当地解决， 该项目的重点是通过基因靶向开发动物模型， 转基因方法，并使用细胞，分子和生物化学 分析各种改变的信号分子对 淋巴细胞在体内的发育、功能和病理。 使用经典的转基因和胚胎干细胞技术， CSK酪氨酸激酶转基因菌株或显性阴性菌株 已经建立了Syk酪氨酸激酶的形式。最小化 转基因表达对动物早期发育的影响 个体发育，采用诱导系统来驱动转基因 表情这些模型系统可以让我们详细研究 参与淋巴细胞发育的细胞内信号传导机制 在一个更符合生理的环境中发挥作用。

Intracellular signalling plays a crucial role in lymphocyte development and function. A panel of molecules involved in signalling has been described and chemical interactions between these molecules documented. However, it remains largely elusive as to whether and how the activation of an individual signalling molecule contributes to various in vivo physiological phenomena such as control of antigen receptor gene rearrangement, repertoire selection, tolerance induction, peripheral lymphocyte activation and maintenance of immune memory. Since these questions can only be properly addressed in an in vivo system, this project focuses on developing animal models by gene targeting and transgenic approaches, and using cellular, molecular and biochemical methods to analyse the impact of various altered signalling molecules on the development, function and pathology of lymphocytes in vivo. Using classic transgenic and embryonic stem cell technologies, mouse strains transgenic for the CSK tyrosine kinase or a dominant negative form of the Syk tyrosine kinase have been established. To minimize the impact of the transgene expression on the development of animals in early ontogeny, an inducible system was employed to drive the transgene expression. These model systems may allow us to study in detail intracellular signalling mechanisms involved in lymphocyte development and function in a more physiological environment.