GENE AND TRANSGENE REGULATION IN THE DEVELOPING MOUSE

晶状体癌的发生和分化。我们培育的老鼠携带有 编码SV40肿瘤抗原的休眠转基因的拷贝。这个 转基因是专门针对晶状体的，并包含一些特征 这使得它们的表达依赖于Cre的作用，一个站点- 特异性噬菌体DNA重组酶。癌基因激活的时间 通过使CRE在之前或同时可用来控制 胚胎晶状体初级纤维分化的开始 水泡。Cre的早期表达导致癌基因的激活 未分化的晶状体上皮细胞在晶状体内快速增殖 镜片胶囊。相比之下，当Cre累积延迟到 与初级晶状体纤维分化的开始相吻合，SV40 癌基因在已经开始伸长的细胞中被激活 积累晶状体特有的晶状体蛋白。在随后的扩散过程中 在晶状体囊内，转化的子代细胞保持了轮廓 它们的亲本细胞在当时获得的纤维分化的 致癌转化的可能性。我们的发现表明，分化的 初始目标单元的状态是后续工作的重要参数 晶状体肿瘤的发生，以及完整的晶状体囊膜可以限制侵袭性 肿瘤生长。LIM基因功能分析已成为一项新的研究课题 研究的重点。LIM基因编码部分功能网络 在后生动物中参与模式形成和细胞规范 发展。它们错综复杂的监管潜力体现在 它们包含三个相邻的监管区域，两个LIM 结构域和一个同源同源结构域。我们已经开始了关于LIM的工作 非洲爪哇同源基因Lim1的克隆和测序 Xlim1基因。这种基因在过去的几年里保存得非常好 进化，在发育中的排泄系统中检测到转录本 以及中枢神经系统。Zeta家族信号转导的作用 T细胞发育中的分子。齐塔人家族二聚体是一组 在结构和功能上相关的蛋白质表达为 T细胞抗原受体复合体的亚基或作为 某些Fc受体。在这两种情况下，它们都促进了配体介导 表面受体与细胞内偶联的信号转导 信号通路。我们已经开始分析齐塔人的角色- 家族二聚体在T细胞个体发育中的作用：1)产生转基因小鼠， 过度表达这些分子中的每一个或过度表达突变形式 Zeta，和2)产生缺乏Zeta的小鼠，Zeta是主要成员 通过同源重组。我们的结果表明 Zeta家族二聚体可以在 但关键的胸腺细胞信号通路是 对这些信号分子有不同的反应。

Lens oncogenesis and differentiation. We generated mice that carry copies of a dormant transgene encoding the SV40 tumor antigens. The transgenes are specifically targeted to the lens and contain features that render their expression dependent on the action of Cre, a site- specific bacteriophage DNA recombinase. Timing of oncogene activation was controlled by making Cre available either prior to, or coincident with, the onset of primary fiber differentiation in the embryonic lens vesicle. Early expression of Cre resulted in oncogene activation in undifferentiated lens epithelial cells that rapidly proliferated inside the lens capsule. By contrast, when Cre accumulation was delayed to coincide with the onset of primary lens fiber differentiation, SV40 oncogenes were activated in cells that had begun to elongate and to accumulate lens-specific crystallins. During subsequent proliferation inside the lens capsule, transformed progeny cells maintained the profile of fiber differentiation that their parent cells had acquired at the time of oncogenic conversion. Our findings show that the differentiated state of the primary target cell is an important parameter of subsequent lens oncogenesis, and that an intact lens capsule can restrict invasive neoplastic growth. The analysis of lim gene function has become a new focus of research. Lim genes encode part of a network of functions involved in pattern formation and cell specification during metazoan development. Their intricate regulatory potential is indicated by the fact that they contain three adjacent regulatory regions, two lim domains and one homeo domain. We have begun our work on the lim genes by cloning and sequencing lim1, a homolog of the Xenopus laevis Xlim1 gene. The gene has been extremely well conserved during evolution, Transcripts are detected in the developing excretory system and in the central nervous system. Role of the Zeta-family signaling molecules in T cell development. The Zeta-family dimers are a group of structurally and functionally related proteins that are expressed as subunits of the T-Cell antigen receptor complex or as subunits of certain Fc receptors. In both contexts, they facilitate ligand-mediated signal transduction by coupling the surface receptor to intracellular signaling pathways. We have begun to analyze the role of the Zeta- family dimers in T-cells ontogeny by: 1) generating transgenic mice that overexpress each of these molecules or the overexpress mutated forms of Zeta, and 2) generating mice that lack Zeta, the predominant member of this group, by homologous-recombination. Our results suggest that the Zeta family dimers can perform complementary functions in development but that critical thymocyte signaling pathways are differentially responsive to these signaling molecules.