%0 Journal Article
%T Large animal models for Huntington's disease research.
%A Han B
%A Liang W
%A Li XJ
%A Li S
%A Yan S
%A Tu Z
%J Zool Res
%V 45
%N 2
%D 2024 Mar 18
%M 38485497
%F 6.975
%R 10.24272/j.issn.2095-8137.2023.199
%X Huntington's disease (HD) is a hereditary neurodegenerative disorder for which there is currently no effective treatment available. Consequently, the development of appropriate disease models is critical to thoroughly investigate disease progression. The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin ( HTT) gene, leading to the expansion of a polyglutamine repeat in the HTT protein. Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain, which precipitate selective neuronal loss in specific brain regions. Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets. Due to the marked species differences between rodents and larger animals, substantial efforts have been directed toward establishing large animal models for HD research. These models are pivotal for advancing the discovery of novel therapeutic targets, enhancing effective drug delivery methods, and improving treatment outcomes. We have explored the advantages of utilizing large animal models, particularly pigs, in previous reviews. Since then, however, significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD. In the current review, we provide a comprehensive overview of large animal models of HD, incorporating recent findings regarding the establishment of HD knock-in (KI) pigs and their genetic therapy. We also explore the utilization of large animal models in HD research, with a focus on sheep, non-human primates (NHPs), and pigs. Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.<BR>亨廷顿舞蹈症(HD)是一种遗传性神经退行性疾病，目前尚无有效的治疗方法。因此，建立合适的动物疾病模型，对疾病进行深入、全面研究非常重要。HD是由亨廷顿( HTT)基因中CAG重复序列的异常扩增（≥36），导致HTT蛋白中多聚谷氨酰胺重复序列的扩增。突变HTT在大脑中发生错误折叠并聚集，导致特定脑区神经元选择性丧失。动物模型在阐明包括HD在内的神经退行性疾病发病机制以及探索潜在的治疗靶点方面发挥着重要作用。鉴于啮齿类动物与人类之间较大的物种差异，因此建立大动物模型是研究HD发病机制的重要手段，这将有助于新治疗靶点的发现，有效的药物递送方法探究，最终改善治疗效果。本综述旨在结合近年来关于HD大动物模型的建立及其基因治疗的研究进展，对HD大动物模型进行更全面的概述。在此我们探讨了大型动物模型，特别是绵羊、非人灵长类动物和猪在亨廷顿研究中的应用。我们期望这些在大动物模型上的发现，为研究和治疗神经退行性疾病提供有价值的见解。.