Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice.
Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice.
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DOI：
10.3791/51275
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发表时间：
2014-04-15
期刊：
影响因子：
--
通讯作者：
Meuth SG
中科院分区：
文献类型：
--
作者：
Bittner S;Afzali AM;Wiendl H;Meuth SG
多发性硬化症是一种中枢神经系统慢性神经炎性脱髓鞘疾病，具有强烈的神经退行性成分。虽然该病的确切病因尚不清楚，但认为自身反应性T淋巴细胞在其病理生理学中起核心作用。到目前为止，MS治疗仅部分有效，研究工作继续扩大我们对疾病病理生理学的了解，并开发新的治疗策略。实验性自身免疫性脑脊髓炎（EAE）是MS最常见的动物模型，具有许多临床和病理生理学特征。存在广泛多样的EAE模型，其反映了人类MS的不同临床、免疫学和组织学方面。小鼠中的主动诱导的EAE是最简单的诱导模型，具有稳健和可复制的结果。它特别适用于研究药物或特定基因的影响，通过使用转基因小鼠受到自身免疫性神经炎症的挑战。因此，用CNS匀浆或髓磷脂蛋白的肽免疫小鼠。由于这些肽的低免疫原性潜力，使用强佐剂。EAE易感性和表型取决于所选抗原和啮齿动物品系。C57 BL/6小鼠是构建转基因小鼠的常用品系，并且尤其对髓鞘少突胶质细胞糖蛋白（MOG）有应答。免疫前将免疫原性表位MOG 35 -55悬浮于完全弗氏佐剂（CFA）中，并在免疫当天和两天后施用百日咳毒素。小鼠在免疫后9-14天内发展为“经典的”自限性双相EAE，具有上行性弛缓性麻痹。每天使用临床评分系统评价小鼠，持续25-50天。特别考虑照顾EAE的动物，以及潜在的应用和这种模式的局限性进行了讨论。
Multiple sclerosis is a chronic neuroinflammatory demyelinating disorder of the central nervous system with a strong neurodegenerative component. While the exact etiology of the disease is yet unclear, autoreactive T lymphocytes are thought to play a central role in its pathophysiology. MS therapy is only partially effective so far and research efforts continue to expand our knowledge on the pathophysiology of the disease and to develop novel treatment strategies. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for MS sharing many clinical and pathophysiological features. There is a broad diversity of EAE models which reflect different clinical, immunological and histological aspects of human MS. Actively-induced EAE in mice is the easiest inducible model with robust and replicable results. It is especially suited for investigating the effects of drugs or of particular genes by using transgenic mice challenged by autoimmune neuroinflammation. Therefore, mice are immunized with CNS homogenates or peptides of myelin proteins. Due to the low immunogenic potential of these peptides, strong adjuvants are used. EAE susceptibility and phenotype depends on the chosen antigen and rodent strain. C57BL/6 mice are the commonly used strain for transgenic mouse construction and respond among others to myelin oligodendrocyte glycoprotein (MOG). The immunogenic epitope MOG35-55 is suspended in complete Freund's adjuvant (CFA) prior to immunization and pertussis toxin is applied on the day of immunization and two days later. Mice develop a "classic" self-limited monophasic EAE with ascending flaccid paralysis within 9-14 days after immunization. Mice are evaluated daily using a clinical scoring system for 25-50 days. Special considerations for care taking of animals with EAE as well as potential applications and limitations of this model are discussed.
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