A TRANSGENIC MONKEY: INHERITED NEURODEGENERATIVE DISEASES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的目标是建立一个亨廷顿病（HD）的转基因猴模型。亨廷顿氏病是由具有延长的多聚谷氨酰胺重复的亨廷顿基因的单基因缺陷引起的。 目的是建立一种转基因非人灵长类动物（NHP）HD模型。 我们已经产生了几种慢病毒载体，携带HD突变体与84和150聚谷氨酰胺重复。这些病毒载体也已经通过转基因小鼠的产生进行了测试。所得到的转基因小鼠具有严重的运动缺陷，并表达HD转基因小鼠的经典表型，如R6/2。我们确信，该相同的构建体将足以在拟定的时间范围内产生具有相当表型的转基因HD猴。我们还成功地用外源性激素刺激雌猴，通过卵胞浆内单精子注射和体外培养实现受精。下一步是将突变基因导入猴卵母细胞，然后在代孕雌性中进行胚胎移植。总之，HD猴模型的生成是可行的。

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.