Genetic architecture of tuberculosis resistance in a mouse model of infection.
Genetic architecture of tuberculosis resistance in a mouse model of infection.
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小鼠感染模型中结核病耐药性的遗传结构。
DOI：
10.1038/sj.gene.6364288
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发表时间：
2006
影响因子：
5
通讯作者：
Kramnik,I
中科院分区：
文献类型：
--
作者：
Yan,B-S;Kirby,A;Shebzukhov,YV;Daly,MJ;Kramnik,I
结核病仍然是一个重大的公共卫生问题：三分之一的人口感染了剧毒结核分枝杆菌 (MTB)，其中 10% 的人在一生中面临患结核病的风险。在人类和实验动物模型中，感染个体之间的遗传变异会影响感染的结果。然而，在免疫功能正常的个体（大多数患者）中，结核病易感性的遗传决定因素仍然很大程度上未知。 MTB 感染的小鼠模型可以控制暴露和其他潜在的环境因素，已被证明对于检查这种遗传成分非常有用。在 C3HeB/FeJ（易感）与 C57BL/6J（耐药）近交小鼠品系的杂交中，我们之前已鉴定出一个主要遗传位点 sst1，其易感等位基因不会导致明显的免疫缺陷，但会特异性影响肺结核的进展。在生成并测试了 sst1 同源菌株后，我们观察到该基因座仅部分解释了亲本菌株对 MTB 敏感性的差异。我们现在提出进一步的研究来控制 sst1 的影响，确定四个额外的结核病易感位点，并通过测试独立的杂交、敲除或同源小鼠来表征它们的影响。
Tuberculosis remains a significant public health problem: one-third of the human population is infected with virulent Mycobacterium tuberculosis (MTB) and 10% of those are at risk of developing tuberculosis during their lifetime. In both humans and experimental animal models, genetic variation among infected individuals contributes to the outcome of infection. However, in immunocompetent individuals (the majority of patients), genetic determinants of susceptibility to tuberculosis remain largely unknown. Mouse models of MTB infection, allowing control of exposure and other potential environmental contributors, have proven extremely useful for examining this genetic component. In a cross of C3HeB/FeJ (susceptible) by C57BL/6J (resistant) inbred mouse strains, we have previously identified one major genetic locus, sst1, the susceptible allele of which did not confer an overt immunodeficiency, but rather specifically affected progression of lung tuberculosis. Having generated and tested the sst1 congenic strains, we have observed that this locus only partially explained the difference in susceptibility of the parental strains to MTB. We now present further studies controlling for the effect of the sst1, identify four additional tuberculosis susceptibility loci and characterize their effects by testing an independent cross, knockout or congenic mice.