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多发性硬化症的小鼠模型:实验性自身免疫性脑脊髓炎和泰勒氏病毒诱导的脱髓鞘疾病。

Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease.

作者信息

McCarthy Derrick P, Richards Maureen H, Miller Stephen D

机构信息

Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

出版信息

Methods Mol Biol. 2012;900:381-401. doi: 10.1007/978-1-60761-720-4_19.

DOI:10.1007/978-1-60761-720-4_19
PMID:22933080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3583382/
Abstract

Experimental autoimmune encephalomyelitis (EAE) and Theiler's Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD) are two clinically relevant murine models of multiple sclerosis (MS). Like MS, both are characterized by mononuclear cell infiltration into the CNS and demyelination. EAE is induced by either the administration of myelin protein or peptide in adjuvant or by the adoptive transfer of encephalitogenic T cell blasts into naïve recipients. The relative merits of each of these protocols are compared. Depending on the type of question being asked, different mouse strains and peptides are used. Different disease courses are observed with different strains and different peptides in active EAE. These variations are also addressed. Additionally, issues relevant to clinical grading of EAE in mice are discussed. In addition to EAE induction, useful references for other disease indicators such as DTH, in vitro proliferation, and immunohistochemistry are provided. TMEV-IDD is a useful model for understanding the possible viral etiology of MS. This section provides detailed information on the preparation of viral stocks and subsequent intracerebral infection of mice. Additionally, virus plaque assay and clinical disease assessment are discussed. Recently, recombinant TMEV strains have been created for the study of molecular mimicry which incorporate various 30 amino acid myelin epitopes within the leader region of TMEV.

摘要

实验性自身免疫性脑脊髓炎(EAE)和泰勒氏鼠脑脊髓炎病毒诱导的脱髓鞘疾病(TMEV-IDD)是多发性硬化症(MS)的两种临床相关小鼠模型。与MS一样,两者的特征都是单核细胞浸润到中枢神经系统并发生脱髓鞘。EAE可通过在佐剂中给予髓磷脂蛋白或肽,或通过将致脑炎性T细胞母细胞过继转移到未致敏的受体中来诱导。比较了每种方案的相对优点。根据所提出问题的类型,使用不同的小鼠品系和肽。在活动性EAE中,不同的品系和不同的肽会观察到不同的病程。这些差异也会得到探讨。此外,还讨论了与小鼠EAE临床分级相关的问题。除了EAE诱导外,还提供了其他疾病指标(如迟发型超敏反应、体外增殖和免疫组织化学)的有用参考文献。TMEV-IDD是理解MS可能的病毒病因的有用模型。本节提供了有关病毒储备液制备以及随后小鼠脑内感染的详细信息。此外,还讨论了病毒蚀斑测定和临床疾病评估。最近,已创建了重组TMEV菌株用于分子模拟研究,这些菌株在TMEV的前导区内整合了各种30个氨基酸的髓磷脂表位。

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