A two years longitudinal study of a transgenic Huntington disease monkey.
A two years longitudinal study of a transgenic Huntington disease monkey.
复制标题
DOI：
10.1186/1471-2202-15-36
复制
发表时间：
2014-03-03
期刊：
影响因子：
2.4
通讯作者：
Bachevalier J
中科院分区：
文献类型：
--
作者：
Chan AW;Xu Y;Jiang J;Rahim T;Zhao D;Kocerha J;Chi T;Moran S;Engelhardt H;Larkin K;Neumann A;Cheng H;Li C;Nelson K;Banta H;Zola SM;Villinger F;Yang J;Testa CM;Mao H;Zhang X;Bachevalier J
对转基因亨廷顿病（HD）猴进行了为期两年的纵向研究，包括形态测量MRI测量和认知行为评价。rHD 1是一种转基因HD猴，表达编码亨廷顿蛋白（HTT）的人基因的外显子1，具有由人多聚泛素C启动子调控的29个CAG重复序列，与4只年龄匹配的野生型对照猴一起使用。这是第一个基于纵向临床测量的人类HD灵长类动物模型的研究。在rHD 1中观察到纹状体和海马体积的变化，伴随运动功能和认知下降的进行性损害，包括学习刺激-奖赏关联、识别记忆和空间记忆的缺陷。结果表明转基因HD猴的纹状体和海马中存在进行性认知下降和形态学变化。这是第一个基于纵向临床测量的人类HD灵长类动物模型的研究。虽然本研究基于单个HD猴，但正在进行的额外HD猴纵向研究对于确认我们的发现非常重要。HD的非人灵长类动物模型可以补充HD的其他动物模型，以更好地了解HD的发病机制和诊断和治疗的未来发展，通过纵向评估。
A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington’s disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.