ESTABLISHMENT OF A TRANSGENIC MONKEY MODEL OF HUNTINGTON?S DISEASE

亨廷顿病转基因猴模型的建立

• 批准号: 8172353
• 负责人: ANTHONY WING SANG CHAN
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172353
• 关键词: Adult; Birth; Blood; CAG repeat; Cell Line; Cognitive; Collection; Computer Retrieval of Information on Scientific Projects Database; Constitution; Cryopreservation; Development; Disease Progression; Evaluation; Exons; Female; Funding; Future; Genes; Genetic; Germ Cells; Grant; Human; Huntington Disease; Institution; Lymphocyte; Magnetic Resonance Imaging; Modeling; Monitor; Monkeys; Plasma; Polyubiquitin; Regulation; Research; Research Personnel; Resources; Source; Techniques; Testing; Transgenic Organisms; United States National Institutes of Health; behavior test; lymphoblast; male; promoter

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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 HD 进展的纵向评估。在这些 HD 猴中，一只 (HD9) 29 个月大，携带 htt 基因的外显子 1，在人多聚泛素-C 启动子的调控下具有 29 个 CAG 重复序列。 另外三只 HD 猴（两只为 17 个月，一只为 15 个月）在人 htt 启动子的调控下携带 512aa 的 htt 片段，其中包含各种 CAG 重复序列（HD14：65；HD16：29、57 和 71；HD17：70）。 除了四只转基因 HD 猴子外，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该研究中，并接受了与 HD 猴相同的测试和治疗，包括所有认知行为测试、每六个月一次 MRI、每月采血（血浆、血清和淋巴细胞库）以及每六个月建立淋巴母细胞系。我们最近分配了四名成年女性和一名男性来开发配子冷冻保存技术。 该项目的目的是继续监测HD猴的HD进展情况，并开发保存HD猴配子的冷冻保存技术，这对于HD猴群体的未来扩张和保存HD猴的遗传构成具有重要意义。