Evidence inconsistent with a role for the Bcg gene (Nramp1) in resistance of mice to infection with virulent Mycobacterium tuberculosis.

Evidence inconsistent with a role for the Bcg gene (Nramp1) in resistance of mice to infection with virulent Mycobacterium tuberculosis.
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证据与 Bcg 基因 (Nramp1) 在小鼠抵抗强毒力结核分枝杆菌感染中的作用不一致。

DOI:
10.1084/jem.183.3.1045
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发表时间:
1996
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
North,RJ
North,RJ
中科院分区:
--
文献类型:
--
作者:
Medina,E;North,RJ

文献摘要

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某些小鼠菌株对某些细胞内病原体(包括牛分枝杆菌疫苗株卡介苗)感染的抗性优于其他菌株,这是由与1号染色体上一个由Ity/Lsh/ BCG位点指定的小片段相关的基因决定的,这里称为BCG位点。采用含有卡介苗基因显性抗性等位基因(Bcgr)的DBA/2小鼠、含有隐性易感等位基因(Bcgs)的主要组织相容性复合物-相容BALB/c小鼠和含有卡介苗位点的先天性c . d2 - n20 Bcgr小鼠,除了具有一小段含有卡介苗位点的DBA/2 1号染色体外,它们在遗传上与BALB/c小鼠相同。根据经静脉或呼吸途径感染的Bcgr和Bcgs小鼠的存活时间,Bcgr小鼠对Mtb感染的抗性比Bcgs小鼠低得多,而不是更高。Bcgr小鼠较短的存活时间与控制结核分枝杆菌在其肺部生长和延缓结核分枝杆菌诱导的该器官病理发展的能力较差有关。对结核分枝杆菌感染的抗性是Bcgr和Bcgs小鼠F1后代的显性性状。结果表明,对结核分枝杆菌的抗性不是由Bcg基因的抗性等位基因决定的,也不是由新近分离到的位于Bcg位点的候选Bcg基因Nramp1决定的。
The superior resistance of some strains of mice over others to infection with certain intracellular pathogens, including the vaccine strain of Mycobacterium bovis, bacillus Calmette Guerin (BCG), is determined by a gene associated with a small segment of chromosome 1 designated by Ity/Lsh/Bcg locus, referred to here as the Bcg locus. DBA/2 mice containing the dominant resistant allele of the Bcg gene (Bcgr), major histocompatibility complex-compatible BALB/c mice containing the recessive susceptible allele (Bcgs), and congenic C.D2-N20 Bcgr, which are genetically the same as BALB/c mice except for possessing a small piece of DBA/2 chromosome 1 containing the Bcg locus, were used to determine whether the Bcg gene determines resistance to infection with the virulent H37Rv strain of Mycobacterium tuberculosis (Mtb). According to the survival times of Bcgr and Bcgs mice infected via either the intravenous or respiratory route, Bcgr mice proved much less, rather than more, resistant to Mtb infection than Bcgs mice. Shorter survival times of Bcgr mice were associated with an inferior capacity to control Mtb growth in their lungs and to retard the development of Mtb-induced pathology in this organ. Resistance to Mtb infection was a dominant trait in the F1 progeny of Bcgr and Bcgs mice. The results show that resistance to Mtb is not determined by the resistance allele of the Bcg gene nor by the recently isolated candidate Bcg gene Nramp1, located in the Bcg locus.