Abedi-Valugerdi M, Hansson M, Möller G
Department of Immunology, the Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden.
Scand J Immunol. 2001 Jul-Aug;54(1-2):190-7. doi: 10.1046/j.1365-3083.2001.00932.x.
Previous studies have shown that genetic factors control the susceptibility to mercury-induced immunoglobulin (Ig)G1 antibody formation, IgE synthesis, renal IgG deposits and antinucleolar autoantibodies (ANolA) production in the susceptible mice. In this study, we examined the genetic control of resistance to these characteristics after HgCl2 injection in F1 hybrid crosses between the highly mercury resistant DBA/2 and mercury susceptible NZB (H-2d), SJL (H-2 s), A.CA (H-2f) and DBA/1 (H-2q) mice and also in backcross hybrids between (DBA/2 x SJL)F1 and SJL mice. We observed that mercury-induced immune/autoimmune manifestations were profoundly downregulated in most (if not all) of the F1 hybrids, indicating that the resistance to mercury was a dominant trait. Analysis of mercury-induced immune/autoimmune responses in the (DBA/2 x SJL) x SJL backcross hybrids suggested that only one gene or a cluster of genes determined the resistance to the ANolA production, whereas the resistance to other characteristics was controlled by two and/or three gene loci. By H-2 genotyping the backcross mice, it was found that H-2d haplotype per se could confer resistance to ANolA production. However, we did not find any significant association between the H-2d haplotype and the resistance to increase of IgG1 and IgE synthesis and the development of renal IgG1 deposits. Thus, while in DBA/2 mice, gene(s) in the H-2 loci strictly contribute to the inheritance of resistance to ANolA production; non-H-2 genes mainly govern the inheritance of unresponsiveness regarding other characteristics.
先前的研究表明，在易感小鼠中，遗传因素控制着对汞诱导的免疫球蛋白（Ig）G1抗体形成、IgE合成、肾脏IgG沉积和抗核仁自身抗体（ANolA）产生的易感性。在本研究中，我们检测了在高度耐汞的DBA/2与汞易感的NZB（H-2d）、SJL（H-2s）、A.CA（H-2f）和DBA/1（H-2q）小鼠之间的F1杂交后代以及（DBA/2×SJL）F1与SJL小鼠的回交杂种中，注射HgCl2后对这些特征的抗性的遗传控制情况。我们观察到，在大多数（如果不是全部）F1杂种中，汞诱导的免疫/自身免疫表现被显著下调，这表明对汞的抗性是一个显性性状。对（DBA/2×SJL）×SJL回交杂种中汞诱导的免疫/自身免疫反应的分析表明，只有一个基因或一组基因决定了对ANolA产生的抗性，而对其他特征的抗性则由两个和/或三个基因位点控制。通过对回交小鼠进行H-2基因分型，发现H-2d单倍型本身可以赋予对ANolA产生的抗性。然而，我们没有发现H-2d单倍型与IgG1和IgE合成增加的抗性以及肾脏IgG1沉积的发展之间存在任何显著关联。因此，在DBA/2小鼠中，H-2基因座中的基因严格地参与了对ANolA产生抗性的遗传；非H-2基因主要控制关于其他特征的无反应性的遗传。
