GENE AND TRANSGENE REGULATION IN THE DEVELOPING MOUSE

透镜肿瘤发生和分化。 在转基因小鼠中，一种休眠的癌基因已经被激活， 原核生物，位点特异性重组酶CRE。癌基因的发生 表达式已被引导以与透镜的特定阶段一致 发展 因此，透镜纤维细胞可以在不同的温度下永生化。 沿着它们的终末分化途径的各个阶段。 nm23在小鼠发育过程中的表达。 nm23的表达已被描述为非转移性肿瘤的标志物。 某些啮齿动物和人类肿瘤的生长特性。 在小鼠 我们检测到高水平的nm23基因， 器官发生 表达似乎局限于上皮组织， 尤其是在发病和终末阶段之间， 分化 这种表达模式与 观察到nm23表达与侵袭性之间的负相关性 上皮来源的肿瘤。 T细胞受体（TCR）zeta链在胸腺细胞发育中的作用。 TCR-ζ链是T细胞抗原 受体复合物和某些Fc受体。 在这两种情况下， 受体表面表达和配体介导的信号所需 转导 为了研究TCR-ζ在T细胞个体发育中的作用， 表达高水平全长或突变形式的转基因小鼠 的zeta链已经产生和分析。 结果提示 zeta介导的信号通路控制早期胸腺细胞 发育事件，如TCR α和β基因重排，和 2)在发育过程中TCR复合物的表面表达受到控制 通过细胞内zeta链的水平。 通过靶向破坏小鼠建立高雪氏病动物模型 葡萄糖脑苷脂酶（GC）基因。 在一个大型的合作实验中，我们产生了一个GC的无效等位基因， 通过在小鼠胚胎干细胞中插入新霉素抗性基因， 染色体靶基因。 将突变的胚胎干细胞注入 进入正常胚泡，并获得嵌合生殖系突变。 GC突变纯合子小鼠的正常GC不到4% 活动，出生后不久死亡，并显示溶酶体储存障碍 与戈谢病患者相似 因此，动物将 对研究人类疾病的发病机理和 评估治疗方法。

Lens oncogenesis and differentiation. A dormant oncogene has been activated in the transgenic mouse via the prokaryotic, site-specific recombinase CRE. The onset of oncogene expression has been directed to coincide with specific stages of lens development. Lens fiber cells can thus be immortalized at distinct stages along their pathway to terminal differentiation. Expression of nm23 during mouse development. The expression of nm23 has been described as a marker of non-metastatic growth properties of certain rodent and human tumors. During mouse development, we detect high levels of the nm23 gene during organogenesis. Expression appears confined to epithelial tissues, and is especially prominent between the onset and the terminal phase of differentiation. This expression pattern correlates well with the inverse relationship between nm23 expression and invasiveness observed in tumors of epithelial origin. Role of the T-cell receptor (TCR) zeta chain in thymocyte development. The TCR-zeta chain is an essential subunit of both the T-cell antigen receptor complex and certain Fc receptors. In both contexts, zeta in required for receptor surface expression and ligand-mediated signal transduction. To examine the role of TCR-zeta in T-cell ontogeny, transgenic mice expressing high levels of full-length or mutated forms of the zeta chain have been generated and analyzed. The results suggest that 1) zeta-mediated signalling pathways control early thymocyte developmental events such as TCR alpha and beta gene rearrangement, and 2) surface expression of TCR complexes during development is controlled by the level of intracellular zeta chain. Animal modal of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase (GC) gene. In a large collaborative experiment, we generated a null allele of GC in murine embryonic stem cells by inserting a neomycin resistance gene in the chromosomal target gene. Mutant embryonic stem cells were injected into normal blastocysts, and a chimeric germ line mutation was obtained. Mice homozygous for the GC mutation have less than 4% of normal GC activity, die shortly after birth and show a lysosomal storage disorder that resembles that of Gaucher patients. The animals will therefore be valuable for investigating the pathogenesis of the human disease and for evaluating therapeutic approaches.