PATHOGENESIS OF AUTOIMMUNITY IN MICE WITH SLE-LIKE ILLNESS

在狼疮易感小鼠品系中，骨髓来源的多能干细胞 细胞和/或它们的直接后代表现出过量的 增殖 他们增加了内源性和 外源性干细胞衍生集落。 NZB骨髓体外研究 证明干细胞来源的B细胞产生过量的IgM， 相对于其他菌株的抗DNA。 结果得到证实， 使用分选纯化的干细胞进行延伸。 此外，这种分拣机 纯化的干细胞将eh NZB表型转移到正常小鼠。 这些 研究表明干细胞活性存在根本性异常。 逆转录病毒研究表明狼疮患者胸腺中存在过量的Mpmv RNA- 俯卧的老鼠 该异常可随骨髓干细胞转移 细胞 对这种异常表达的基础进行了研究。 第一、 用Mpmv特异性探针探测来自NZB小鼠的基因组文库， 分离的全长克隆。 对LTR进行了测序，证明了LTR是一个 负调控区的突变。 凝胶阻滞研究 证实突变改变了调节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 colonies. In vitro studies with NZB marrow demonstrate an excess of 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 eh 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 transferrable 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.