CORE--TRANSGENIC MOUSE FACILITY

这项计划拨款反映了一个概念和技术交织在一起， 一系列的实验来了解细胞信号的生物学， 阐明了信号扰动的分子事件 途径可能导致正常细胞转化为恶性细胞， 表型观察到恶性表型稳定 遗传，导致了大量基因的鉴定 参与细胞信号传导，其改变的表达导致细胞 转型分子生物学和遗传学的新技术 能够产生特定原癌基因突变的小鼠， 以及异常表达这些基因的转基因小鼠的产生， 基因，现在允许分析这些遗传元件的功能 在一个组织层面上。这提供了新的和重要的见解， 这些基因在正常发育中的作用，以及 其功能的改变可导致恶性转化。作为 因此，该计划中的建议在很大程度上依赖于基因 涉及通过同源基因靶向的小鼠的操作 重组或产生转基因小鼠。

This Program grant reflects a conceptually and technically intertwined series of experiments to understand the biology of cell signaling and to elucidate the molecular events by which perturbations in signaling pathways may lead to the conversion of a normal cell to the malignant phenotype. The observation that the malignant phenotype is stably inherited, has lead to the identification of a vast array of genes involved in cell signaling whose altered expression leads to cellular transformation. New technologies in molecular biology and genetics, the ability to generate mice with mutations in specific proto-oncogenes, as well as the generation of transgenic mice aberrantly expressing these genes, now permits an analysis of the function of these genetic elements at an organismic level. This has provided new and significant insight into the role of these genes in normal development, and the way in which alteration in their function may lead to malignant transformation. As such, the proposals in this program rely heavily on the genetic manipulation of mice involving either gene targeting by homologous recombination or the generation of transgenic mice.