Turcotte K, Loredo-Osti J C, Fortin P, Schurr E, Morgan K, Gros P
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Genes Immun. 2006 Dec;7(8):684-7. doi: 10.1038/sj.gene.6364346. Epub 2006 Oct 5.
Susceptibility to Mycobacterium bovis Bacille Calmette-Guérin (BCG) is genetically controlled by Nramp1 (Slc11a1). Inbred mouse strains harbor either the resistance (Nramp1(G169)) or the susceptibility (Nramp1(D169)) allele at Nramp1. Mus spretus (Nramp1(G169); SPRET/EiJ) is shown to display an intermediate level of BCG replication in the spleen (log(10) colony-forming units (CFU) approximately 5), compared to resistant A/J (log(10)CFU approximately 4.0) and susceptible C57BL/6J (log(10)CFU approximately 6.0) mice. The presence of genetic modifiers of Nramp1-dependent susceptibility to M. bovis (BCG) infection in Mus spretus was analyzed by whole-genome scanning in 175 mice of an informative (C57BL/6J x SPRET/EiJ) x C57BL/6J backcross. Nramp1 showed a major effect (D1Mcg4, P<1e(-4)), but additional single marker effects were identified on chromosomes 4 (D4Mit150) and x (DXMit249) in male mice, and on chromosome 9 (D9Mit77) and 17 (D17Mit81) in female mice. A strong interaction between Nramp1 and the major histocompatibility locus was also noted in female mice. The mapped loci may act as modifiers of Nramp1 action, and constitute novel entry points for the parallel search of loci regulating susceptibility to mycobacterial infections in humans.
对牛分枝杆菌卡介苗（BCG）的易感性由Nramp1（Slc11a1）进行基因控制。近交系小鼠品系在Nramp1位点携带抗性（Nramp1(G169)）或易感（Nramp1(D169)）等位基因。与抗性A/J小鼠（log(10)集落形成单位（CFU）约为4.0）和易感C57BL/6J小鼠（log(10)CFU约为6.0）相比，小家鼠（Nramp1(G169); SPRET/EiJ）在脾脏中显示出中等水平的BCG复制（log(10)CFU约为5）。通过对175只信息丰富的（C57BL/6J×SPRET/EiJ）×C57BL/6J回交小鼠进行全基因组扫描，分析了小家鼠中Nramp1依赖性对牛分枝杆菌（BCG）感染易感性的遗传修饰因子的存在情况。Nramp1显示出主要作用（D1Mcg4，P<1e(-4)），但在雄性小鼠的4号染色体（D4Mit150）和X染色体（DXMit249）以及雌性小鼠的9号染色体（D9Mit77）和17号染色体（D17Mit81）上鉴定出了额外的单标记效应。在雌性小鼠中还注意到Nramp1与主要组织相容性位点之间存在强烈的相互作用。定位的基因座可能作为Nramp1作用的修饰因子，并构成平行搜索调节人类对分枝杆菌感染易感性的基因座的新切入点。
