ESTABLISHMENT OF A TRANSGENIC MONKEY MODEL OF HUNTINGTON?S DISEASE

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。 我们已经建立了四只转基因亨廷顿病(HD)猴子和四只野生型非转基因猴子，用于纵向评估HD的进展。在这些HD猴中，有一只(HD9)是29个月大的，在人类多泛素-C启动子的调控下携带HTT基因的外显子1，有29个CAG重复。 另外三只HD猴(两只17个月，一只15个月)在人类HTT启动子的调控下携带一段512aa的HTT片段，带有不同的CAG重复序列(HD14：65；HD16：29，57和71；以及HD17：70)。除了四只转基因HD猴外，我们还有两只雄性和两只雌性野生型非转基因猴子作为对照。它们在出生后不久就被分配到这项研究中，并接受了与HD猴子相同的测试和治疗，包括所有认知行为测试、每六个月一次的MRI、每月采血(血浆、血清和淋巴细胞库)，以及每六个月建立一次淋巴母细胞系。最近，我们指派了四名成年女性和一名男性来开发配子冷冻保存技术。 该项目的目标是继续监测HD猴子的进展情况，并开发一种用于保存HD猴子配子的冷冻保存技术，这对未来扩大HD猴子群体和保存HD猴子的遗传构成非常重要。

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. We have established four transgenic Huntington's disease (HD) monkey founders and four wild-type non-transgenic monkeys for longitudinal evaluation of HD progression. Among these HD monkeys, one (HD9) is 29 months old and carries an Exon 1 of htt gene with 29 CAG repeats under the regulation of a human polyubiquitin-C promoter. The other three HD monkeys (two are seventeen months and one is fifteen months) carry an htt fragment of 512aa with various CAG repeats (HD14: 65; HD16: 29, 57 and 71; and HD17: 70) under the regulation of a human htt promoter. In addition to the four transgenic HD monkeys, we had two male and two female wild-type non-transgenic monkeys serving as controls. They were assigned to the study shortly after birth and have received identical testing and treatment as the HD monkeys, including all cognitive behavioral tests, MRI every six months, monthly blood collection (plasma, serum and lymphocyte bank), and the establishment of lymphoblast cell lines every six months. We recently assigned four adult females and one male for the development of a gamete cryopreservation technique. The objective of the project is to continue monitoring the progression of HD in the HD monkeys and the development of a cryopreservation technique for preserving gametes of HD monkeys, which is important for future expansion of the HD monkey colony and preserving the genetic constitution of the HD monkeys.