Malaria Liver Stage Susceptibility Locus Identified on Mouse Chromosome 17 by Congenic Mapping
Malaria Liver Stage Susceptibility Locus Identified on Mouse Chromosome 17 by Congenic Mapping
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DOI：
10.1371/journal.pone.0001874
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发表时间：
2008-03-26
期刊：
影响因子：
3.7
通讯作者：
Penha-Goncalves, Carlos
中科院分区：
文献类型：
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作者：
Goncalves, Ligia Antunes;Almeida, Paulo;Penha-Goncalves, Carlos
已知宿主遗传变异赋予对疟原虫血液期感染的抗性，并控制人类和小鼠的疟疾严重程度。这项工作描述了一个基因座的遗传图谱的抗性肝阶段寄生虫在小鼠。首先，我们表明，在BALB/c小鼠品系的伯氏疟原虫的肝脏阶段的易感性降低是由于肝内因素和血液阶段感染的初始阶段的影响。我们使用QTL定位技术，以确定一个位点控制这种易感性表型（LOD得分4.2）的小鼠17号染色体（belr 1位点）。此外，同源小鼠品系的分析划定了belr 1位点的边界远端的H2区。感染的同类小鼠肝脏中寄生虫的定量强烈表明，belr 1基因座代表控制伯氏疟原虫在肝组织中扩张的遗传因子。belr 1位点的映射提出了宿主基因变异能够控制疟原虫肝期感染进展的假设，并打开了人类基因组区域直向同源物belr 1可能含有赋予人类疟疾肝期抗性的基因的可能性。
Host genetic variants are known to confer resistance to Plasmodium blood stage infection and to control malaria severity both in humans and mice. This work describes the genetic mapping of a locus for resistance to liver stage parasite in the mouse. First, we show that decreased susceptibility to the liver stage of Plasmodium berghei in the BALB/c mouse strain is attributable to intra-hepatic factors and impacts on the initial phase of blood stage infection. We used QTL mapping techniques to identify a locus controlling this susceptibility phenotype (LOD score 4.2) on mouse chromosome 17 (belr1 locus). Furthermore, analysis of congenic mouse strains delimited the belr1 locus boundaries distally to the H2 region. Quantification of parasites in the liver of infected congenic mice strongly suggested that the belr1 locus represents a genetic factor controlling the expansion of P. berghei in the hepatic tissue. The mapping of belr1 locus raises the hypothesis that host gene variation is able to control the progression of Plasmodium liver stage infection and opens the possibility that the human genomic region orthologue to belr1 may contain genes that confer resistance to the human malaria liver stage.