Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease.
Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease.
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DOI：
10.4049/jimmunol.162.2.948
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发表时间：
1999-01
影响因子：
4.4
通讯作者：
J. Weis;B. McCracken;Ying Ma;Daryl Fairbairn;R. Roper;Tom B. Morrison;J. Weis;J. Zachary;R. Doerge;C. Teuscher
中科院分区：
文献类型：
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作者：
J. Weis;B. McCracken;Ying Ma;Daryl Fairbairn;R. Roper;Tom B. Morrison;J. Weis;J. Zachary;R. Doerge;C. Teuscher
在莱姆病患者中观察到一系列疾病严重程度，约60%未经治疗的个体发生关节炎。莱姆病的鼠模型提供了强有力的证据，表明宿主的遗传组成影响感染伯氏疏螺旋体后关节炎的严重程度：感染的C3 H小鼠发展为严重的关节炎，而感染的C57 BL/6 N小鼠发展为轻度关节炎。在B期间控制关节炎严重程度和体液反应的小鼠基因组区域。在C3 H/HeNCr和C57 BL/6 NCr杂交F2代小鼠中发现了伯氏螺旋体感染。后踝肿胀测量确定了4号和5号染色体上的数量性状位点（QTL），而组织病理学评分确定了5号染色体和11号染色体上的一个独特区域上的QTL。对踝关节肿胀或组织病理学严重程度的QTL的鉴定表明，在不同的遗传控制下的过程是莱姆病关节炎这两种表现的原因。控制由B诱导的循环Ig水平的另外的QTL。在6、9、11、12和17号染色体上鉴定出伯氏螺旋体感染。有趣的是，体液反应的大小与感染F2小鼠关节炎的严重程度无关。这项工作定义了几个基因位点，调节关节炎的严重程度或对B的体液反应的大小。burgdorferi感染的小鼠，对理解宿主与病原体的相互作用参与疾病的发展。
A spectrum of disease severity has been observed in patients with Lyme disease, with approximately 60% of untreated individuals developing arthritis. The murine model of Lyme disease has provided strong evidence that the genetic composition of the host influences the severity of arthritis following infection with Borrelia burgdorferi: infected C3H mice develop severe arthritis while infected C57BL/6N mice develop mild arthritis. Regions of the mouse genome controlling arthritis severity and humoral responses during B. burgdorferi infection were identified in the F2 intercross generation of C3H/HeNCr and C57BL/6NCr mice. Rear ankle swelling measurements identified quantitative trait loci (QTL) on chromosomes 4 and 5, while histopathological scoring identified QTL on a unique region of chromosome 5 and on chromosome 11. The identification of QTL unique for ankle swelling or histopathological severity suggests that processes under distinct genetic control are responsible for these two manifestations of Lyme arthritis. Additional QTL that control the levels of circulating Igs induced by B. burgdorferi infection were identified on chromosomes 6, 9, 11, 12, and 17. Interestingly, the magnitude of the humoral response was not correlated with the severity of arthritis in infected F2 mice. This work defines several genetic loci that regulate either the severity of arthritis or the magnitude of humoral responses to B. burgdorferi infection in mice, with implications toward understanding the host-pathogen interactions involved in disease development.