Genetic Modifiers Of Autoimmune Disease In FcgammaRIIB M

我们已经为缺乏FcGammaRIIB的小鼠建立了一种新的系统性自身免疫性疾病模型，FcGammaRIIB是一种免疫球蛋白结合受体，可抑制抗体产生和炎症反应。这些小鼠会发展出一种自发性疾病，类似于人类的狼疮，但只在特定的遗传背景下发生。我们的目标是确定导致该系统背景差异的易感/耐药基因座。我们对来自一个抗性品系和一个狼疮敏感品系杂交的200只小鼠进行了分析，发现了三个新的抗性基因座。已经产生了新的小鼠品系，在这些品系中，这些抗性基因被转移到RII-/-B6背景，以便进一步进行遗传定位和最终的基因鉴定。在对倾向于自身免疫的RII-/-B6小鼠的特征描述中，我们观察到，通过与某些修饰品系杂交，它们的疾病可以加重或减弱。我们在RII-/-B6YAA小鼠中观察到与自身抗体特异性改变相关的增强疾病。通过比较这些新的疾病模型，我们旨在剖析自身免疫病理学的要求。这些新发现的基因可能会发现修改狼疮或其他自身免疫性疾病正在进行的疾病的潜在途径，并将作为疾病易感性、进展和严重程度的预测因子。

We have generated a new model for systemic autoimmune disease in mice deficient in FcgammaRIIB, an IgG-binding receptor that inhibits antibody production and inflammatory responses. These mice develop a spontaneous disease that resembles lupus in humans but only in certain genetic backgrounds. Our goal is to identify susceptibility/resistance genetic loci that are responsible for the background differences in this system. We have performed an analysis of 200 mice derived from the cross between a resistant strain and a lupus susceptible strain and have identified three new resistance loci. New mouse lines have been generated in which these resistance loci are transferred to the RII-/-B6 background to allow further genetic mapping and eventual gene identification. In the characterization of the autoimmune-prone RII-/-B6 mice, we have observed that they can be aggravated or attenuated in their disease by crossing to certain modifier strains. We have observed enhanced disease in RII-/- B6 Yaa mice that correlates with a change in autoantibody specificity. By comparing these new models of disease we aim to dissect the requirements for the autoimmune pathology. These newly discovered genes will possibly uncover potential routes for modifying ongoing disease in lupus or other autoimmune diseases and will serve as predictors of disease susceptibility, progression and severity.