TRANSGENIC APPROACHES TO NERVOUS SYSTEM DEVELOPMENT

转基因小鼠提供了一种攻击复杂系统的新方法 比如神经系统。多方面指导的方法 走向研究干扰神经元的后果 开发和功能正在开发中。作为第一步， 编码儿茶酚胺相关酶的四个基因 生物合成将被克隆，以表征神经元- 这些基因中每一个都有特定的增强子和启动子元件。 以帮助理解允许表达的DNA元素 神经元亚群中的这些基因，来自神经元的增强剂- 在所有神经元中表达的特定烯醇化酶基因也将被 特色化的。来自这些的增强子/启动子元件 基因将被用来指导各种结构蛋白的表达 特异性神经元和肾上腺髓质细胞的基因 转基因小鼠。结构基因将被选择为可能影响 神经细胞发育或功能的各个方面。他们 可以分为几个类别。(I)癌基因：SV40T- 抗原、ras、myc和/或src对神经元分化的影响 将对转型进行研究。(Ii)神经生长因子： 神经元生长、分化和存活的假说 都受到NGF梯度的影响将得到测试。(Iii) 神经递质：转基因小鼠体内特定亚群的神经递质 神经元表达额外的神经递质或神经调节 将创建多肽以确定是否会改变 神经递质合成影响发育和功能 神经系统的一部分。(四)白喉毒素：此毒素将 用于消融产生肾上腺素的肾上腺髓质细胞以 研究肾上腺素在应激反应中的作用。它也将是 用来研究删除神经元造成的后果 特定的神经递质对其余部分的发育 神经系统。

Transgenic mice offer a new approach to attack complex systems such as the nervous system. A multi-faceted approach directed towards studying the consequences of interfering with neuron development and function is being developed. As first step, the four genes encoding the enzymes involved in catecholamine biosynthesis will be cloned in order to characterize the neuron- specific enhancer and promoter elements in each of these genes. To help understand the DNA elements that allow expression of these genes in subsets of neurons, the enhancers from the neuron- specific enolase gene, that is expressed in all neurons, will also be characterized. The enhancer/promoter elements from these genes will be used to direct the expression of various structural genes to specific neurons and adrenal medullary cells of transgenic mice. Structural genes will be chosen that may affect various aspects of neuronal cell development or function. They fall into several categories. (i) Oncogenes: The effect of SV40 T- antigen, ras, myc and /or src on neuronal differentiation or transformation will be studied. (ii) Nerve growth factor (NGF): The hypothesis that neuronal growth, differentiation and survival are influenced by gradients of NGF will be tested. (iii) Neurotransmitters: Transgenic mice in which specific subsets of neurons express additional neurotransmitters or neuromodulatory peptides will be created to determine whether altering neurotransmitter synthesis affects the development and function of the nervous system. (iv) Diphtheria toxin: This toxin will be used to ablate epinephrine-producing adrenal medullary cells to study the role of epinephrine in stress response. It will also be used to study the consequences of deleting neurons making a specific neurotransmitter on the development of the rest of the nervous system.