Abstract：
The knowledge about the contribution of the innate immune system to health and disease is expanding. However, to obtain reliable results, it is critical to select appropriate mouse models for in vivo studies. Data on genetic and phenotypic changes associated with different mouse strains can assist in this task. Such data can also facilitate our understanding of how specific polymorphisms and genetic alterations affect gene function, phenotypes, and disease outcomes. Extensive information is available on genetic changes in all major mouse strains. However, comparatively little is known about their impact on immune response and in particular on innate immunity. Here, we analyzed a mouse model of chronic multifocal osteomyelitis (CMO), an autoinflammatory disease driven exclusively by the innate immune system, which is caused by an inactivating mutation in the Pstpip2 gene. We investigated how the genetic background of BALB/c, C57BL/6J, and C57BL/6NCrl strains alters the molecular mechanisms controlling disease progression. While all mice developed the disease, symptoms were significantly milder in BALB/c and partially also in C57BL/6J when compared to C57BL/6NCrl. Disease severity correlated with the number of infiltrating neutrophils and monocytes and with the production of chemokines attracting these cells to the site of inflammation. It also correlated with increased expression of genes associated with autoinflammation, rheumatoid arthritis, neutrophil activation, and degranulation, resulting in altered neutrophil activation in vivo. Together, our data demonstrate striking effects of genetic background on multiple parameters of neutrophil function and activity influencing the onset and course of the CMO disease.
摘要：
关于先天免疫系统对健康和疾病的贡献的知识正在扩大。然而,为了获得可靠的结果，选择合适的小鼠模型进行体内研究是至关重要的。与不同小鼠品系相关的遗传和表型变化的数据可以帮助完成这项任务。这些数据还可以帮助我们理解特定的多态性和遗传改变如何影响基因功能。表型，和疾病结果。关于所有主要小鼠品系的遗传变化的广泛信息是可用的。然而,人们对它们对免疫反应，特别是先天免疫的影响知之甚少。这里,我们分析了慢性多灶性骨髓炎（CMO）的小鼠模型，一种完全由先天免疫系统驱动的自身炎性疾病，这是由Pstpip2基因的失活突变引起的。我们调查了BALB/c的遗传背景，C57BL/6J,和C57BL/6NCrl菌株改变了控制疾病进展的分子机制。虽然所有的老鼠都患上了这种疾病，与C57BL/6NCrl相比，BALB/c的症状明显减轻，C57BL/6J的症状也部分减轻。疾病严重程度与浸润的嗜中性粒细胞和单核细胞的数量以及将这些细胞吸引到炎症部位的趋化因子的产生相关。它还与自身炎症相关基因的表达增加有关，类风湿性关节炎,中性粒细胞激活，和脱粒，导致体内中性粒细胞活化改变。一起,我们的数据表明,遗传背景对影响CMO疾病发病和病程的中性粒细胞功能和活动的多个参数有显著影响.
