A TRANSGENIC MONKEY: INHERITED NEURODEGENERATIVE DISEASES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目标是建立亨廷顿病(HD)的转基因猴子模型。亨廷顿氏病是由亨廷顿蛋白基因的单一基因缺陷与延长的多谷氨酰胺重复引起的。目的是建立一种转基因非人灵长类(NHP)HD模型。我们已经产生了几个慢病毒载体，携带带有84和150个多谷氨酰胺重复的HD突变体。这些病毒载体也通过创造转基因小鼠进行了测试。得到的转基因小鼠有严重的运动缺陷，并表达典型的HD转基因小鼠的表型，如R6/2。我们相信，在建议的时间框架内，相同的构建将足以产生具有类似表型的转基因HD猴子。我们还成功地用外源激素刺激雌性猴子，通过卵胞浆内单精子注射和随后的体外培养实现受精。下一步是将突变基因导入猴卵母细胞，然后进行代孕雌性胚胎移植。综上所述，建立HD猴模型是可行的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The project goal is to establish a transgenic monkey model of Huntington's Disease (HD). Huntington's Disease is caused by a single gene defect of the huntingtin gene with extended polyglutamine repeats. The objective is to develop a transgenic nonhuman primate (NHP) model for HD. We have generated several lentiviral vectors that carry the HD mutant with 84 and 150 polyglutamine repeat. These viral vectors have also been tested by the creation of transgenic mice. The resulted transgenic mice have severe motor deficiency and expressed classical phenotype of HD transgenic mice such as the R6/2. We are confident that this same construct will be sufficient to generate transgenic HD monkey with comparable phenotypes at proposed time frame. We have also been successful in stimulating female monkey using exogenous hormone, achieve fertilization by intracytoplasmic sperm injection and followed by in vitro culture. The next step is to introduce the mutant gene into monkey oocyte and followed by embryo transfer in surrogate female. In conclusion, the generation of a HD monkey model is feasible.