GENE AND TRANSGENE REGULATION IN THE DEVELOPING MOUSE

哺乳动物发育、分化和分化的分子遗传学 肿瘤发生项目的这一部分包含两种方法。 A.同源异型盒基因和myc基因。这些家族编码的因子 基因与胚胎发育的转录调控有关， 发展胚胎组织切片和整体的原位杂交 聚合酶链反应分析显示， 不同的空间和时间表达模式的几个成员， 这些基因。同源盒基因和myc基因家族都可能是 参与协调小鼠早期发育的各个方面。 目前，我们试图通过同源的方法引入有缺陷的DNA序列， 多能小鼠胚胎特异性靶基因的重组 干细胞在特定染色体上产生突变 基因.如果成功，这种实验将证实 同源异型盒，myc和其他基因家族参与 小鼠发育的调控。它也可以用来生成鼠标 人类遗传疾病的模型。B。分化和肿瘤发生 转基因小鼠的眼睛透镜。我们利用了简单的架构 的眼睛透镜开发一个模型系统的分析放松管制 在活的哺乳动物有机体中生长。多瘤的癌基因产物和 在小鼠发育的特定时间在透镜组织中释放的SV 40病毒 导致明显的透镜病变。我们的发现使我们能够 提出了一个工作模型，假设表达的时间和表达的时间都是有限的。 给定致癌基因产物的剂量对于随后的 增长放松管制的步骤。 生物医学研究。在我们项目的这一部分，我们已经确定了 胎盘是一个非常活跃的器官， 转基因小鼠中的启动子。这一结果具有重要意义 对感染艾滋病毒的母亲所生子女进行风险评估， 人体免疫机能丧失病毒。同时，我们已经开始探索 在转基因农场动物的牛奶中产生大量的组织 纤溶酶原激活剂和sCD 4，治疗冠状动脉粥样硬化所需的人类蛋白质 疾病和艾滋病。

Molecular genetics of mammalian development, differentiation and oncogenesis. This part of the project contains two approaches. A. Homeobox genes and myc genes. Factors encoded by these families of genes have been implicated in the transcriptional regulation of embryonic development. In situ hybridization of embryonic tissue sections and whole mounts of embryos with polymerase chain reaction analysis have revealed distinct spatial and temporal patterns of expression of several members of these genes. Both the homeobox and the myc gene families are likely to be involved in orchestrating individual facets of early mouse development. Presently, we attempt to introduce defective DNA sequences via homologous recombination into specific target genes of pluripotent mouse embryonic stem cells in an effort to generate mutations in specific chromosomal genes. If successful, this type of experiment will corroborate genetic evidence for the involvement of homeobox, myc, and other gene families in the regulation of mouse development. It can also be used to generate mouse models of human genetic diseases. B. Differentiation and oncogenesis in the eye lens of transgenic mice. We have utilized the simple architecture of the eye lens to develop a model system for the analysis of deregulated growth in the living mammalian organism. Oncogene products of polyoma and SV40 virus released in lens tissue at specific times of mouse development result in distinct lens pathologies. Our findings have allowed us to propose a working model postulating that both timing of expression and the dose of a given oncogene product are of crucial importance for subsequent steps of growth deregulation. Biomedical research. In this part of our project, we have identified the placenta as an organ that is very active in recognizing AIDS virus promoters in the transgenic mouse. This result has important implications for the risk assessment for children born to mothers infected with the human immunodeficiency virus. Also, we have begun to exploit possibilities of producing in milk of transgenic farm animals large amounts of tissue plasminogen activator and of sCD4, human proteins needed to treat coronary diseases and AIDS, respectively.