Drescher Kristen M, Sosnowska Danuta
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
Front Biosci. 2008 May 1;13:3775-85. doi: 10.2741/2966.
Choosing an appropriate animal model to study a disease is guided by a variety of factors including but not limited to the questions being asked, availability of reagents, knowledge of the animal species, personal biases of the researcher, and in some cases, cost and availability of facilities to effectively investigate the model. The validity of an animal model can be further complicated when the etiology of the disease is incompletely defined. Examples of these diseases include multiple sclerosis (MS) and type 1 diabetes (T1D). In addition to host genetics, epidemiological studies have implicated infectious agents, in particular viruses as triggers of these diseases. Thus many studies of these diseases have focused on modeling the interactions of viruses and the host immune response in vivo in small animals. Theiler's murine encephalomyelitis virus (TMEV) infection of mice has been used for over 30 years as a model of virus-induced demyelination. TMEV induces a MS-like disease in susceptible strains of mice but does not cause pathology in humans. While some researchers may question the rationale for using a non-human pathogen to model human disease, the TMEV model of central nervous system (CNS) demyelination has permitted study of some aspects of human MS which would have been difficult to address in other models of the disease. Despite being 'merely a disease of mice,' many of the findings in the Theiler's virus model are directly applicable to the human condition, and studies from the model are responsible for our current understanding of mechanisms of pathology and clinical disability in human MS. In this review we will present some of the key findings from the TMEV model in the context of human disease.
选择合适的动物模型来研究疾病受到多种因素的指导，这些因素包括但不限于所提出的问题、试剂的可获得性、对动物物种的了解、研究人员的个人偏见，在某些情况下，还包括有效研究该模型的成本和设施的可获得性。当疾病的病因尚未完全明确时，动物模型的有效性可能会变得更加复杂。这些疾病的例子包括多发性硬化症（MS）和1型糖尿病（T1D）。除了宿主遗传学外，流行病学研究表明感染因子，特别是病毒是这些疾病的触发因素。因此，许多针对这些疾病的研究都集中在模拟病毒与宿主免疫反应在小型动物体内的相互作用。小鼠感染泰勒氏鼠脑脊髓炎病毒（TMEV）作为病毒诱导脱髓鞘的模型已经使用了30多年。TMEV在易感小鼠品系中诱发类似MS的疾病，但不会在人类中引起病变。虽然一些研究人员可能会质疑使用非人类病原体来模拟人类疾病的合理性，但中枢神经系统（CNS）脱髓鞘的TMEV模型允许研究人类MS的某些方面，而这些方面在该疾病的其他模型中很难解决。尽管泰勒氏病毒模型“仅仅是小鼠的疾病”，但该模型中的许多发现都直接适用于人类情况，并且该模型的研究促成了我们目前对人类MS病理机制和临床残疾的理解。在这篇综述中，我们将在人类疾病的背景下介绍TMEV模型的一些关键发现。
