PATHOGENESIS OF AUTOIMMUNITY IN MICE WITH SLE-LIKE ILLNESS

在易患狼疮的小鼠中，骨髓来源的多能干细胞 细胞和/或其直系后代表现出过度 扩散。他们增加了内源性和 外源干细胞来源的B细胞产生IgM和抗DNA 相对于其他菌株。结果得到了证实和推广使用 分选器纯化的干细胞。此外，这种分选器提纯了干细胞 将NZB表型转移给正常小鼠。这些研究表明， 干细胞活性的根本异常。 逆转录病毒研究显示狼疮胸腺中存在过量的MPMV RNA- 易受攻击的老鼠。这种异常可以与骨髓干细胞转移。 对这种反常表达的基础进行了研究。首先，一个 用Mpmv特异性探针和DNA探针对NZB小鼠基因组文库进行了探索。 已分离出全长克隆。对LTR进行了测序，证明了 负调控区域的突变。凝胶延迟研究 确认突变改变了调节性DNA结合的结合 蛋白。

IN lupus-prone strains of mice, bone marrow derived pluripotent stem cells and/or their immediate progeny demonstrate excessive proliferation. They have increased numbers of both endogenous and exogenous stem cell derived B cell production of IgM and anti-DNA relative to other strains. The results were confirmed and extended using sorter purified stem cells. In addition, such sorter purified stem cells transfer the NZB phenotype to normal mice. These studies suggest a fundamental abnormality in stem cell activity. Retrovirus studies demonstrate excess Mpmv RNA in thymuses of lupus- prone mice. The abnormality is transferable with bone marrow stem cells. The basis for this abnormal expression has been studied. First, a genomic library from NZB mice was probed with Mpmv specific probes and a full-length clone isolated. The LTR was sequenced, demonstrating a mutation in a negative regulatory region. Gel retardation studies confirm that the mutation alters binding of a regulatory DNA binding protein.