IN VIVO ANALYSIS OF INTRACELLULAR SIGNALS CONTROLLING LYMPHOCYTE

细胞内信号在淋巴细胞发育中起着至关重要的作用 和功能。一组参与信号传递的分子已经 描述了这些分子之间的相互作用，并记录了它们之间的化学作用。 然而，激活是否以及如何激活在很大程度上仍然难以捉摸。 单个信号分子在体内对不同的 抗原受体基因调控等生理现象 重排、曲目选择、耐受性诱导、外围设备 淋巴细胞的激活和免疫记忆的维持。因为这些 只有在活体系统中才能恰当地解决问题，这 该项目专注于通过基因打靶和 转基因方法，并使用细胞、分子和生化 分析各种信号分子改变对细胞周期的影响的方法 体内淋巴细胞的发育、功能和病理。 利用经典的转基因和胚胎干细胞技术，小鼠 转CSK酪氨酸激酶或显性阴性的菌株 Syk酪氨酸激酶的形式已经建立。要最小化 转基因表达对动物早期发育的影响 在个体发育过程中，利用诱导系统驱动转基因。 表情。这些模型系统可能使我们能够详细研究 参与淋巴细胞发育的细胞内信号机制 并在更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.