CNRS, Immunopathologie et chimie thérapeutique/Laboratory of excellence Medalis, Institut de Biologie Moléculaire et Cellulaire, 67000 Strasbourg, France.
Autoimmun Rev. 2014 Sep;13(9):963-73. doi: 10.1016/j.autrev.2014.08.015. Epub 2014 Aug 23.
Mouse models of autoimmunity, such as (NZB×NZW)F1, MRL/MpJ-Fas(lpr) (MRL-lpr) and BXSB mice, spontaneously develop systemic lupus erythematosus (SLE)-like syndromes with heterogeneity and complexity that characterize human SLE. Despite their inherent limitations, such models have highly contributed to our current understanding of the pathogenesis of SLE as they provide powerful tools to approach the human disease at the genetic, cellular, molecular and environmental levels. They also allow novel treatment strategies to be evaluated in a complex integrated system, a favorable context knowing that very few murine models that adequately mimic human autoimmune diseases exist. As we move forward with more efficient medications to treat lupus patients, certain forms of the disease that requires to be better understood at the mechanistic level emerge. This is the case of neuropsychiatric (NP) events that affect 50-60% at SLE onset or within the first year after SLE diagnosis. Intense research performed at deciphering NP features in lupus mouse models has been undertaken. It is central to develop the first lead molecules aimed at specifically treating NPSLE. Here we discuss how mouse models, and most particularly MRL-lpr female mice, can be used for studying the pathogenesis of NPSLE in an animal setting, what are the NP symptoms that develop, and how they compare with human SLE, and, with a critical view, what are the neurobehavioral tests that are pertinent for evaluating the degree of altered functions and the progresses resulting from potentially active therapeutics.
自身免疫性疾病的小鼠模型，如（NZB×NZW）F1、MRL/MpJ-Fas(lpr)（MRL-lpr）和 BXSB 小鼠，会自发地发展出具有异质性和复杂性的系统性红斑狼疮（SLE）样综合征，这些特征与人类 SLE 相似。尽管这些模型存在固有局限性，但它们对我们目前对 SLE 发病机制的理解做出了重要贡献，因为它们为我们提供了在遗传、细胞、分子和环境水平上研究人类疾病的有力工具。这些模型还允许在复杂的综合系统中评估新的治疗策略，这在了解到很少有能够充分模拟人类自身免疫性疾病的小鼠模型的情况下是一个有利的背景。随着我们开发出更有效的药物来治疗狼疮患者，某些需要在机制水平上更好地理解的疾病形式也逐渐显现出来。神经精神（NP）事件就是这种情况，它会影响 50-60%的 SLE 患者在发病时或 SLE 诊断后的第一年。在狼疮小鼠模型中对 NP 特征进行破译的研究已经进行了大量的研究。开发针对 NPSLE 的首批先导分子至关重要。在这里，我们讨论了如何在动物模型中使用小鼠模型，特别是 MRL-lpr 雌性小鼠，来研究 NPSLE 的发病机制，会出现哪些 NP 症状，以及它们与人类 SLE 有何不同，以及从批判性的角度来看，哪些神经行为测试对于评估功能改变的程度和潜在有效治疗的进展是相关的。
