Jacob C O, McDevitt H O
Department of Medical Microbiology, Stanford University School of Medicine, California 94306.
Nature. 1988 Jan 28;331(6154):356-8. doi: 10.1038/331356a0.
The (NZB x NZW)F1 hybrid mouse develops a severe autoimmune disease similar to systemic lupus erythematosus in humans. Both the human and murine form of the disease show strong associations with alleles of the major histocompatibility complex (MHC) gene products. The severe form of the disease found in F1 mice is due, in part, to dominant NZW gene(s) mapping with the H-2 complex (the murine MHC). Here we present evidence that the tumour necrosis factor (TNF-alpha) gene, which is located within the H-2 complex (the murine major histocompatibility complex), could be involved in the pathogenesis of lupus nephritis in F1 mice. Thus, a restriction fragment length polymorphism in the TNF-alpha gene correlates with the reduced levels of TNF-alpha produced by NZW mice. Furthermore, replacement therapy with recombinant TNF-alpha induces a significant delay in the development of the nephritis.
（新西兰黑鼠×新西兰白鼠）F1杂交小鼠会患上一种严重的自身免疫性疾病，类似于人类的系统性红斑狼疮。这种疾病在人类和小鼠中的形式都与主要组织相容性复合体（MHC）基因产物的等位基因有很强的关联。在F1小鼠中发现的严重疾病形式部分归因于与H-2复合体（小鼠MHC）连锁的显性NZW基因。我们在此提供证据表明，位于H-2复合体（小鼠主要组织相容性复合体）内的肿瘤坏死因子（TNF-α）基因可能参与F1小鼠狼疮性肾炎的发病机制。因此，TNF-α基因中的限制性片段长度多态性与NZW小鼠产生的TNF-α水平降低相关。此外，用重组TNF-α进行替代疗法可显著延迟肾炎的发展。
