A TRANSGENIC MONKEY: INHERITED NEURODEGENERATIVE DISEASES

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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.