CONTROL OF N-CAM BY HOX AND PAX GENES IN TRANSGENIC MICE

细胞黏附分子在胚胎组织中发挥着重要作用。 以及维持成人组织的结构和功能。中的更改 CaM的表达伴随着许多疾病状态，它已经被证明 它们既参与再生过程又参与退化过程 包括神经和肌肉。我们建议研究凸轮的功能在 将鸡肝基因显微注射到小鼠胚胎体内 细胞黏附分子L-CAM在启动子的调控下会引起 它将在转基因小鼠中表达，在L-CAM不存在的位置 通常都能看到。此外，我们正在建造L- 通常不会看到凸轮。此外，我们还构建了 截断、突变和删除神经细胞的内源性基因 黏附分子N-CAM，通过胚胎干细胞和 移植到小鼠的囊胚中产生转基因小鼠。 鸡L-CAM基因与胰岛素偶联的DNA构建 启动子、神经丝启动子和晶体蛋白启动子已经被 用于这个实验室的初步实验，以制造转基因小鼠。 胰岛素启动子启动子在鸡β细胞中表达L细胞黏附分子 胰腺的细胞功能出现了一些明显的扰动。中国的文化 ES细胞已经建立，小鼠N-CAM基因组克隆已经建立 与世隔绝。异位表达L-细胞黏附分子小鼠的建立 组织特异性启动子应提供局部干扰的机会 L细胞黏附分子在胰腺β细胞和神经元中的表达 在晶状体细胞中。这些组织不正常表达L-CAM，但表达 其他凸轮，可以评估。我们的初步研究表明，一些 这些动物存活下来，可以用来寻找L-CAM对 再生过程(例如神经-肌肉相互作用)和退行性 伴随着衰老的过程。内源性的改变或消融 N-CAM基因应详细分析每种形式的作用 处于体内发育、再生和退化过程中的分子。这些 研究应该对各种出生缺陷有广泛的影响 和遗传缺陷，并为评估其作用提供重要数据 与老化相关的事件中的凸轮。

Cell adhesion molecules (CAMs) play important roles in embryonic tissues and in maintaining the structure and function of adult tissues. Changes in CAM expression accompany a number of disease states, and it has been shown that they are involved in both regenerative and degenerative processes including nerve and muscle. We propose to study the function of CAMs in vivo by microinjecting into mouse embryos the gene for the chicken liver cell adhesion molecule L-CAM under the control of promoters that will cause it to be expressed in transgenic mice in locations where L-CAM is not normally seen. In addition we are making constructs to locations where L- CAM is not normally seen. In addition we are making constructs to truncate, mutate, and delete the endogenous gene for the neural cell adhesion molecule, N-CAM, by transfection of embryonicstem (ES) cells and transplantation into mouse blastocysts to produce transgenic mice. DNA constructs that include the chicken L-CAM gene coupled to the insulin promoter, the neurofilament promoter, and the crystallin promoter have been used in initial experiments in this laboratory to make transgenic mice. Those with the insulin promoter express chicken L-CAM in the beta-cells of the pancreas with some apparent perturbation of cell function. Cultures of ES cells have been established and mouse N-CAM genomic clones have been isolated. Production of mice ectopically expressing L-CAM under control of tissue specific promoters should provide opportunities to locally perturb function by L-CAM expression in the beta-cells of the pancreas, in neurons and in lens cells. These tissues do not express L-CAM normally but express other CAMs, can be assessed. Our preliminary studies show that some of these animals survive and can be used to look for the influence of L-CAM on regenerative processes (eg. nerve-muscle interactions) and degenerative processes that accompany aging. Alteration or ablation of the endogenous N-CAM gene should provide a detailed analysis of the role of each form of the molecule in development, regeneration, and degeneration in vivo. These studies should have extensive implications for a variety of birth defects and genetic defects, and provide important data for assessing the role of CAMs in events associated with aging.