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

细胞粘附分子在胚胎组织中起着重要作用 以及维持成人组织的结构和功能。 变化 CAM表达伴随许多疾病状态，并且已经显示 它们参与了再生和退化过程 包括神经和肌肉。 我们建议研究CAM的功能， 通过显微注射到小鼠胚胎中， 细胞粘附分子L-CAM在启动子的控制下， 它将在转基因小鼠中表达，在L-CAM不表达的地方， 正常看。 此外，我们正在构建的位置，L- CAM是不常见的。 此外，我们正在构建 截短、突变和删除神经细胞的内源基因 粘附分子，N-CAM，通过转染胚胎干细胞（ES细胞）， 移植到小鼠胚泡中以产生转基因小鼠。 包括与胰岛素偶联的鸡L-CAM基因的DNA构建体 启动子、神经丝启动子和晶体蛋白启动子已经被广泛应用于临床。 在这个实验室的最初实验中使用，以制造转基因小鼠。 那些具有胰岛素启动子的基因在小鼠的β细胞中表达鸡L-CAM， 胰腺细胞功能出现明显紊乱 文化 已经建立了ES细胞，并且已经克隆了小鼠N-CAM基因组克隆。 与世隔绝 在控制下异位表达L-CAM的小鼠的产生 组织特异性启动子应该提供局部干扰的机会， 通过胰腺β细胞、神经元中的L-CAM表达发挥作用 和透镜细胞中。 这些组织不正常表达L-CAM，但表达 其他的CAMs可以评估。 我们的初步研究表明， 这些动物存活下来，并可用于寻找L-CAM对 再生过程（例如，神经-肌肉相互作用）和退行性 伴随衰老的过程。 内源性的改变或消融 N-CAM基因应提供每种形式的作用的详细分析， 体内发育、再生和退化的分子。 这些 研究应该对各种出生缺陷有广泛的意义， 和遗传缺陷，并提供重要的数据，评估的作用， 与衰老相关的事件中的CAM。

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.