Seetharamaiah Gattadahalli S, Land Kimberly J
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, Indiana 47712, USA.
Thyroid. 2006 Jul;16(7):651-8. doi: 10.1089/thy.2006.16.651.
BALB/c mice are susceptible to the induction of Graves' hyperthyroidism. To investigate the susceptibility of BALB/c substrains of mice to the induction of hyperthyroidism, we immunized BALB/cJ and BALB/cByJ mice with an adenovirus expressing amino acid residues 1-289 of thyrotropin receptor (TSHR). The data presented in this article showed that 17 of 26 (65%) BALB/c and only 4 of 30 (13%) BALB/cBy mice developed hyperthyroidism. Hyperthyroid mice displayed characteristics of Graves' disease, such as thyroid-stimulating antibodies and enlarged thyroid glands. To explore the differences in the susceptibility of these substrains for hyperthyroidism, we examined the TSHR antibodies in three different assays. The TSHR antibodies determined in a radioreceptor assay (TSH binding inhibitory immunoglobulins) were similar in both of these BALB/c substrains. The TSHR antibody titers of total IgG, IgG1, and IgG2a were measured by an enzyme-linked immunosorbent assay and were found to be similar in these mice. There were no significant differences between these two groups of mice in the thyroid-stimulating antibody activity. However, BALB/cBy mice had significantly higher TSH-blocking antibody activity compared to BALB/c mice. TSHR-specific proliferation of splenocytes and secretion of cytokines interferon-gamma and interleukin-4 by spleen cells were comparable in both the groups. BALB/cJ and BALB/cByJ mice both belong to same MHC haplotype, H-2(d), but differ in the Qa-2 region of class Ib molecule. This report shows the importance of other genes, such as Qa-2 region of class Ib molecule in addition to MHC class II, in the susceptibility of Graves' hyperthyroidism.
BALB/c小鼠易被诱导发生格雷夫斯氏甲状腺功能亢进症。为了研究BALB/c小鼠亚系对甲状腺功能亢进症诱导的易感性，我们用表达促甲状腺激素受体（TSHR）第1 - 289个氨基酸残基的腺病毒免疫BALB/cJ和BALB/cByJ小鼠。本文呈现的数据表明，26只BALB/c小鼠中有17只（65%）发生了甲状腺功能亢进症，而30只BALB/cBy小鼠中只有4只（13%）发生了甲状腺功能亢进症。甲状腺功能亢进症小鼠表现出格雷夫斯氏病的特征，如促甲状腺激素刺激抗体和甲状腺肿大。为了探究这些亚系对甲状腺功能亢进症易感性的差异，我们通过三种不同的检测方法检测了TSHR抗体。在放射受体检测（TSH结合抑制性免疫球蛋白）中测定的TSHR抗体在这两个BALB/c亚系中相似。通过酶联免疫吸附测定法测量总IgG、IgG1和IgG2a的TSHR抗体滴度，发现这些小鼠中的滴度相似。这两组小鼠在促甲状腺激素刺激抗体活性方面没有显著差异。然而，与BALB/c小鼠相比，BALB/cBy小鼠具有显著更高的TSH阻断抗体活性。两组中脾细胞的TSHR特异性增殖以及脾细胞分泌细胞因子干扰素-γ和白细胞介素-4的情况相当。BALB/cJ和BALB/cByJ小鼠都属于相同的MHC单倍型H-2(d)，但在Ib类分子的Qa-2区域存在差异。本报告显示了除MHC II类分子外其他基因，如Ib类分子的Qa-2区域，在格雷夫斯氏甲状腺功能亢进症易感性中的重要性。
