Jafarian-Tehrani M, Gabellec M M, Adyel F Z, Simon D, Griffais R, Ternynck T, Haour F
Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
J Neuroimmunol. 1998 Apr 1;84(1):30-9. doi: 10.1016/s0165-5728(97)00239-7.
Interleukin-1 receptor (IL-1R) deficiency has been previously described in the dentate gyrus of autoimmune NZB and (NZB x NZW) F1 (or BWF1) mice. In this study, the genetic and molecular characterization of this defect were investigated in BWF2 mice in relation to anti-DNA antibody production and microsatellite D1Nds4 (near the IL1r1 gene) polymorphism. IL-1R density was quantified in the brain, spleen and pancreas, using in vitro quantitative autoradiography with recombinant human [125I]-IL-1alpha as the ligand. This study of the dentate gyrus of F2 mice revealed three phenotypes: NZW-like, NZB-like and F1-like, which occurred in a ratio of 1:1:2, with IL-1R densities of 100%, 17% and 59%, respectively as compared to control NZW mice (100%). In contrast, IL-1R densities observed in the choroid plexus and peripheral organs were similar. Moreover a high production of IgG2a anti-DNA antibodies was observed in F2 mice, as in their parents, particularly those with the NZB-like phenotype. Microsatellite mapping of D1Nds4 revealed polymorphism in both parents and BWF2 mice in relation to the level of IL-1R density in the dentate gyrus. In spite of the acute defect in IL-1 binding in the dentate gyrus of NZB mice, molecular analysis of IL-1R mRNA (type I, II and accessory protein) showed similar amounts of mRNA, measured following RT-PCR amplification, in the hippocampal formation of both NZB and control C3H/He mice. In conclusion, the transmission of the IL-1R defect in the dentate gyrus of NZB mice is monofactorial and the defect appears to be at the post-transcriptional level of IL-1R synthesis. The lack of IL-1R in the dentate gyrus seems to correlate with some autoimmune characteristics. Correlation of D1Nds4 polymorphism with the level of IL-1R density suggests that it could be a predisposing gene to disease or a marker for other closely linked predisposing genes.
白细胞介素 -1 受体（IL -1R）缺陷先前已在自身免疫性新西兰黑鼠（NZB）和（NZB×NZW）F1（或 BWF1）小鼠的齿状回中被描述。在本研究中，针对 BWF2 小鼠中该缺陷的遗传和分子特征进行了研究，涉及抗 DNA 抗体产生以及微卫星 D1Nds4（靠近 IL1r1 基因）多态性。使用重组人[125I]-IL -1α作为配体的体外定量放射自显影技术，对脑、脾和胰腺中的 IL -1R 密度进行了定量分析。对 F2 小鼠齿状回的这项研究揭示了三种表型：类似 NZW 的、类似 NZB 的和类似 F1 的，其出现比例为 1:1:2，与对照 NZW 小鼠（100%）相比，IL -1R 密度分别为 100%、17%和 59%。相比之下，脉络丛和外周器官中观察到的 IL -1R 密度相似。此外，与它们的亲本一样，尤其是具有类似 NZB 表型的 F2 小鼠中观察到了高产量的 IgG2a 抗 DNA 抗体。D1Nds4 的微卫星图谱显示，亲本和 BWF2 小鼠在齿状回中 IL -1R 密度水平方面存在多态性。尽管 NZB 小鼠齿状回中 IL -1 结合存在急性缺陷，但对 IL -1R mRNA（I 型、II 型和辅助蛋白）的分子分析显示，在 NZB 小鼠和对照 C3H/He 小鼠的海马结构中，经 RT -PCR 扩增后测量的 mRNA 量相似。总之，NZB 小鼠齿状回中 IL -1R 缺陷的传递是单因素的，且该缺陷似乎发生在 IL -1R 合成的转录后水平。齿状回中 IL -1R 的缺乏似乎与一些自身免疫特征相关。D1Nds4 多态性与 IL -1R 密度水平的相关性表明，它可能是疾病的易感基因或其他紧密连锁的易感基因的标志物。
