Development of spontaneous arthritis in β2-micro globulin-deficient mice without expression of HLA-B27 -: Association with deficiency of endogenous major histocompatibility complex class I expression
Development of spontaneous arthritis in β2-micro globulin-deficient mice without expression of HLA-B27 -: Association with deficiency of endogenous major histocompatibility complex class I expression
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DOI：
10.1002/1529-0131(200010)43:10
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发表时间：
2000-10-01
影响因子：
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通讯作者：
Colbert, RA
中科院分区：
文献类型：
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作者：
Kingsbury, DJ;Mear, JP;Colbert, RA
Objective.据报道，β（2）-微球蛋白（β（2）m）缺陷但表达人类主要组织相容性复合体（MHC）I类分子HLA-B27的小鼠会发生自发性炎性关节炎（SA）。我们试图确定在某些条件下，β（2）m缺陷是否足以引起SA，以及这是否可能是I类缺陷的结果。产生以下类型的小鼠：在几种遗传背景下，MHC B单倍型β（2）m（β（2）m（o））遗传缺陷的小鼠（C57 BL/6 J [B6]、BALB/cJ、SJL/J、MRL/MpJ和B6，129），B6背景下抗原加工相关转运蛋白缺陷小鼠（TAP 1（0）），129，和B6背景下的HLA-B27转基因β（2）m（o）小鼠。将队列从无特定病原体（SPF）转移到常规（非SPF）动物室，并对SA的发展进行临床和组织学评价，结果。SA发生在具有混合B6，129基因组的TAP 1（o）和beta（2）m（o）/I类缺陷小鼠中，频率为30- 50%，而10-15%的B6、SJL/J和BALB/cJ beta（2）m（o）小鼠发生这种关节病，MRL/ MPJ beta（2）m（o）小鼠不受影响。与β 2 m（o）B6对照组相比，B27转基因β 2 m（o）B6小鼠SA的发生率并没有增加。I类缺陷足以引起小鼠中的SA。疾病的频率以及B27特异性SA明显依赖于非MHC遗传背景。这些结果表明，在遗传易感小鼠的I类缺陷可以模仿B27相关的关节病。
Objective. Mice deficient in beta(2)-microglobulin (beta(2)m), but expressing the human major histocompatibility complex (MHC) class I molecule HLA-B27, have been reported to develop spontaneous inflammatory arthritis (SA), We sought to determine whether, under certain conditions, beta(2)m deficiency alone was sufficient to cause SA, and if this might be a result of class I deficiency.Methods. The following types of mice were produced: mice of the MHC b haplotype genetically deficient in beta(2)m (beta(2)m(o)) on several genetic backgrounds (C57BL/6J [B6], BALB/cJ, SJL/J, MRL/MpJ, and B6,129), mice deficient in the transporter associated with antigen processing (TAP1(0)) on a B6,129 background, and HLA-B27-transgenic beta(2)m(o) mice on a B6 background. Cohorts were transferred from specific pathogen-free (SPF) to conventional (non-SPF) animal rooms, and evaluated clinically and histologically for the development of SA,Results. SA occurred in TAP1(o) and beta(2)m(o)/class I-deficient mice with a mixed B6,129 genome at a frequency of 30-50%, while 10-15% of B6, SJL/J, and BALB/cJ beta(2)m(o) mice developed this arthropathy, MRL/ MPJ beta(2)m(o) mice were unaffected. Expression of B27 did not increase the frequency of SA in B27-transgenic beta(2)m(o) B6 mice compared with that in beta(2)m(o) B6 controls.Conclusion. Class I deficiency is sufficient to cause SA in mice. The frequency of disease, as well as B27-specific SA, is markedly dependent on a non-MHC genetic background. These results suggest that class I deficiency in a genetically susceptible mouse can mimic B27-associated arthropathy.