亨廷顿病是一种多聚谷氨酰胺异常延伸引发的神经退行性疾病。在人类染色体4p 16.3的IT15基因上，当外显子1起始区附近的CAG重复次数异常增加时，就会导致亨廷顿病。亨廷顿病人的纹状体和皮层会发生神经元的退行和死亡，随后引发一系列运动、精神和认知相关的症状，其中以运动障碍为典型。临床上亨廷顿病仍是不可治愈的。而基因治疗则是有望在此取得突破的疗法之一。通过刻画基因治疗后小鼠的运动表型来评估基因治疗的效果，对于CRISPR-Cas9介导的HD临床前治疗研究具有重要作用。 研究中，对已经进行了AAV9介导的CRISPR-Cas9基因治疗的BAC226Q小鼠进行运动表型的刻画。旷场试验和转杆试验的结果显示治疗的效果有限。重新优化脑立体定位注射的位点以及注射病毒的剂量后，希望在后续的表型刻画中能获得更为明显的治疗效果。

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine extensions. The abnormally increased number of CAG repeat has been proved to be the direct reasons of HD genetically. CAG repeat is close to the axon 1 start coden, which is located in human chromosome 4p 16.3, gene site IT15. Huntington’s patients may suffer a series of motor, mental and cognitive symptoms, especially severe motor dysfunction, because of the degeneration or death of neuron in the striatum and brain cortex. Huntington’s disease is temporarily incurable in clinical. Luckily, gene therapy has been giving us hope as a breakthrough in HD treatment. In this research, the AAV9 mediated CRISPR - Cas9 gene therapy in BAC226Q mice was conducted. To profile the motor phenotype, we conducted the open field test and rota-rod test, the results of which showed that the effect of this treatment was still limited. We optimized the sites and dosage of brain stereotaxic AAV injection. Hopefully, we could get subsequent phenotypic characterization which can indicate the significant rescue of HD mouse model phenotypes in gene therapy.