Identification of the Plasmodium berghei resistance locus 9 linked to survival on chromosome 9.
Identification of the Plasmodium berghei resistance locus 9 linked to survival on chromosome 9.
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DOI：
10.1186/1475-2875-12-316
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发表时间：
2013-09-11
期刊：
影响因子：
3
通讯作者：
Winzeler EA
中科院分区：
文献类型：
--
作者：
Bopp SE;Rodrigo E;González-Páez GE;Frazer M;Barnes SW;Valim C;Watson J;Walker JR;Schmedt C;Winzeler EA
恶性疟原虫感染中严重疟疾死亡的主要原因之一是脑型疟疾（CM）。一个重要的宿主遗传成分决定了个体发展CM或清除感染并成为半免疫的易感性。因此，鉴定与易感性或抗性相关的遗传基因座可用于调节疾病的严重程度。伯氏疟原虫小鼠模型的实验性脑型疟疾（ECM）再现几种疾病的症状，在人类CM中看到的，和两种不同的表型，易感（FVB/NJ）和耐药小鼠品系（DBA/2 J），进行了检查。FVB/NJ小鼠在10天内死于感染，而DBA/2 J小鼠显示出性别偏见：雄性小鼠平均存活19天，雌性小鼠要么因ECM迹象而早期死亡，要么存活长达3周。FVB/NJ和DBA/2 J之间的脑病理学比较显示，在脑出血或微血管中寄生虫和CD 3+细胞数量方面无重大差异。然而，在感染小鼠的外周血中发现了显著差异：例如，在第七天，抗性DBA/2 J小鼠的循环嗜碱性粒细胞数量显著高于FVB/NJ小鼠。对DBA/2 J和FVB/NJ小鼠杂交的F2后代的分析将潜在存活性状的遗传基因座定位到9号染色体，Lod评分为4.9。该位点与先前从血液阶段疟疾模型中鉴定的两个抗性位点（char 1和pymr）重叠。FVB/NJ和DBA/2 J小鼠之间的存活率最能区分疟疾感染。证实了9号染色体上的char 1和pymr在疟疾对伯氏疟原虫的抗性中的重要性。此外，嗜碱性粒细胞数量与生存率相关。
One of the main causes of mortality from severe malaria in Plasmodium falciparum infections is cerebral malaria (CM). An important host genetic component determines the susceptibility of an individual to develop CM or to clear the infection and become semi-immune. As such, the identification of genetic loci associated with susceptibility or resistance may serve to modulate disease severity. The Plasmodium berghei mouse model for experimental cerebral malaria (ECM) reproduces several disease symptoms seen in human CM, and two different phenotypes, a susceptible (FVB/NJ) and a resistant mouse strain (DBA/2J), were examined. FVB/NJ mice died from infection within ten days, whereas DBA/2J mice showed a gender bias: males survived on average nineteen days and females either died early with signs of ECM or survived for up to three weeks. A comparison of brain pathology between FVB/NJ and DBA/2J showed no major differences with regard to brain haemorrhages or the number of parasites and CD3+ cells in the microvasculature. However, significant differences were found in the peripheral blood of infected mice: For example resistant DBA/2J mice had significantly higher numbers of circulating basophils than did FVB/NJ mice on day seven. Analysis of the F2 offspring from a cross of DBA/2J and FVB/NJ mice mapped the genetic locus of the underlying survival trait to chromosome 9 with a Lod score of 4.9. This locus overlaps with two previously identified resistance loci (char1 and pymr) from a blood stage malaria model. Survival best distinguishes malaria infections between FVB/NJ and DBA/2J mice. The importance of char1 and pymr on chromosome 9 in malaria resistance to P. berghei was confirmed. In addition there was an association of basophil numbers with survival.
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影响因子：
5
作者：
Berghout, J.;Min-Oo, G.;Gros, P.
通讯作者：
Gros, P.
影响因子：
3.7
作者：
Goncalves, Ligia Antunes;Almeida, Paulo;Penha-Goncalves, Carlos
通讯作者：
Penha-Goncalves, Carlos
影响因子：
4.4
作者：
Kim, Sohee;Shen, Tao;Min, Booki
通讯作者：
Min, Booki
DOI：
10.4269/ajtmh.1992.46.391
发表时间：
1992-04-01
影响因子：
3.3
作者：
AIKAWA, M;BROWN, A;WEBSTER, K
通讯作者：
WEBSTER, K
影响因子：
3.7
作者：
Bopp SE;Ramachandran V;Henson K;Luzader A;Lindstrom M;Spooner M;Steffy BM;Suzuki O;Janse C;Waters AP;Zhou Y;Wiltshire T;Winzeler EA
通讯作者：
Winzeler EA