Genetic Modifiers Of Autoimmune Disease In FcgammaRIIB

我们已经为缺乏FcgammaRIIB（一种抑制抗体产生和炎症反应的igg结合受体）的小鼠建立了一个系统性自身免疫性疾病的新模型。这些老鼠患上了一种自发的疾病，类似于人类的狼疮，但只是在某些遗传背景下。我们的目标是确定导致该系统背景差异的易感/抗性遗传位点。我们对200只小鼠进行了分析，这些小鼠来自一种耐药菌株和一种狼疮易感菌株的杂交，并确定了三个新的耐药位点。已经产生了新的小鼠系，其中这些抗性位点被转移到RII-/- b6背景中，从而允许进一步的遗传作图和最终的基因鉴定。在对自身免疫易感性RII-/- b6小鼠的表征中，我们观察到，通过与某些修饰菌株杂交，它们的疾病可以加重或减轻。我们观察到RII-/- B6 Yaa小鼠的疾病增强与自身抗体特异性的变化相关。通过比较这些疾病的新模型，我们旨在剖析自身免疫病理的要求。这些新发现的基因可能会发现潜在的途径来改变狼疮或其他自身免疫性疾病的持续疾病，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.