TRANSGENIC ANIMAL MODELS OF HUMAN INHERITED DISORDERS

在许多情况下，自然发生的人类遗传的动物模型 疾病，特别是那些影响神经系统的疾病， 介绍了 在那些已经确定基因缺陷的情况下， 将突变引入小鼠的生殖系可以提供 产生具有适当表型的小鼠的独特机会，其中 可以研究疾病的发病机理和治疗方法。 转基因小鼠 通过将原核DNA显微注射到受精卵中 并通过引入基因修饰的鼠 胚胎干细胞转化为囊胚期小鼠胚胎。 此外 对于“无效等位基因”或“敲除”小鼠的产生， 正在开发用于将微妙的突变引入 小鼠的生殖系。转基因小鼠的基因控制下 细胞（包括神经胶质和神经元）或组织特异性 诱导型/阻遏型启动子也在研究中，特别是 关于神经系统中的基因表达。 的鼠模型 影响神经系统的遗传性疾病 使用这些技术，以及发育和组织特异性 在这些转基因小鼠中表征基因的表达。 我们 协同努力产生人类的转基因小鼠模型 疾病提供了有价值的工具， 影响神经系统的疾病和评价新的 治疗，包括蛋白质/酶替代，细胞 移植和基因转移疗法。

In many cases naturally occurring animal models of human inherited disorders, especially those affecting the nervous system, have not been described. In those cases where the gene defect has been identified, the introduction of mutations into the germ line of mice can provide a unique opportunity to generate mice having appropriate phenotypes where disease pathogenesis and treatment can be studied. Transgenic mice are generated by both pronuclear microinjection of DNA into fertilized eggs and by gene targeting by introduction of genetically modified murine embryonic stem cells into blastocyst stage mouse embryos. In addition to the generation of "null allele" or "knockout" mice, other techniques are being developed for the introduction of subtle mutations into the germline of mice. Transgenic mice with genes under the control of cell(including glia and neuronal) or tissue specific inducible/repressible promoters are also under study, particularly with respect to gene expression in the nervous system. Murine models of inherited disorders affecting the nervous system are being produced using these techniques, and the developmental and tissue specific expression of genes is characterized in these transgenic mice. Our collaborative efforts to generate transgenic mouse models of human disorders are providing valuable tools extending our understanding of disorders affecting the nervous system and for the evaluation of new treatments, including protein/enzyme replacement, cellular transplantation, and gene transfer therapies.