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。尽管大量的信号分子具有 目前还有待阐明的是，激活一种 个体信号分子在体内对各种不同的 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 只有在不同的活体系统中才能正确地解决问题， 该项目致力于利用基因打靶技术开发动物模型。 和转基因方法，然后使用各种细胞、分子 并用生化方法分析各种变化的影响 信号转导通路在肿瘤发生、功能和病理中的作用 体内的淋巴细胞。 我们目前对了解监管职能感兴趣。 蛋白酪氨酸激酶，如CTK，以及所谓的 接头信号分子包括Grb2和c-CBL。因为这个原因， 我们已经建立了几个动物模型，在这些模型中，这些分子 在生殖系或可能处于不同阶段的失活 动物的发育。到目前为止，CTK-/-，c-CBL-/-，Grb2-/和Grb2 我们实验室已经获得了小鼠。这些模型系统可能 使我们能够详细研究所涉及的细胞内信号机制 在淋巴细胞的发育和功能上更具生理性 情况。

Intracellular signaling plays a crucial role in lymphocyte development and function. Although a large number of signaling molecules have identified, it remains to be elucidated how the activation of an individual signaling 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 different in vivo systems, this project focuses on developing animal models using gene targeting and transgenic approaches, and then using various cellular, molecular and biochemical methods to analyze the impact of various altered signaling pathway on the development, function and pathology of lymphocytes in vivo. We are currently interested in understanding the regulatory functions of the protein tyrosine kinases such as Ctk, as well as the so called adaptor signaling molecules including Grb2 and c-cbl. For this reason, we have established several animal models in which these molecules are inactivated either in the germline or potentially at different stages of animal development. So far, Ctk-/-, c-cbl-/-, Grb2-/+ and Grb2floxed mice have been obtained in our laboratory. These model systems may allow us to study in detail intracellular signaling mechanisms involved in lymphocyte development and function in a more physiological situation.