Genetic control of resistance to Trypanosoma brucei brucei infection in mice.
Genetic control of resistance to Trypanosoma brucei brucei infection in mice.
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对小鼠抗性锥虫的抗性的遗传控制。
DOI：
10.1371/journal.pntd.0001173
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发表时间：
2011-06
影响因子：
3.8
通讯作者：
Lipoldová M
中科院分区：
文献类型：
--
作者：
Síma M;Havelková H;Quan L;Svobodová M;Jarošíková T;Vojtíšková J;Stassen AP;Demant P;Lipoldová M
布鲁氏锥虫感染牲畜，对马和狗有严重影响。小鼠品系对这种寄生虫的易感性差别很大。然而，控制这些差异的基因没有被定位。我们利用具有较高定位能力的重组同源（RC）菌株研究了布鲁氏杆菌感染后存活的遗传控制。每个BALB/c-c-STS/A （CcS/Dem）系列的RC菌株含有不同的随机子集，其中12.5%的基因来自亲本“供体”菌株STS/A， 87.5%的基因来自“背景”菌株BALB/c。虽然BALB/c和STS/A小鼠对布鲁氏杆菌的易感相似，但RC菌株CcS-11比它们更易感。我们分析了BALB/c和CcS-11之间感染布鲁氏杆菌的F2杂交体的存活遗传学。CcS-11菌株在8条染色体上携带sts衍生片段。在F2杂交小鼠中进行基因分型，并通过方差分析检验其与生存的联系。我们绘制了四个影响布氏锥虫感染后存活的Tbbr（布氏锥虫反应）位点。Tbbr1（3号染色体）和Tbbr2（12号染色体）对生存的影响独立于基因间相互作用（主要影响）。Tbbr3（7号染色体）与Tbbr4（19号染色体）相互作用影响生存。Tbbr2位于一个短2.15 Mb的片段上，仅包含26个基因。本研究首次鉴定出控制布氏杆菌感染易感性的染色体位点。在近交系F2杂交株中，定位精度通常为40-80 Mb，而在RC株中，我们将Tbbr2定位到2.15 Mb的片段，仅包含26个基因，这将使候选基因的搜索变得有效。对易感基因的定义将提高对该疾病的途径和遗传多样性的理解，并可能产生新的策略来克服布鲁氏杆菌对免疫系统的主动颠覆。布鲁氏锥虫是通过采采蝇传播给哺乳动物宿主的细胞外原生动物。他们开发了几种破坏宿主免疫防御的机制。因此，分析影响宿主抗感染能力的基因可以揭示宿主-寄生虫相互作用的关键方面。布鲁氏锥虫感染许多动物物种，包括牲畜，对马和狗的影响特别严重。小鼠品系对布氏杆菌的易感性差异很大。然而，控制这种寄生虫易感性的基因尚未被定位。采用cc /Dem重组同源（RC）菌株，在BALB/c遗传背景下，每个菌株随机含有供体亲本菌株STS/ a的12.5%基因，分析了布鲁氏杆菌感染后存活的遗传控制。RC菌株CcS-11甚至比BALB/c或STS/A更容易感染寄生虫。在BALB/c和CcS-11的F2杂交体中，我们检测并绘制了控制布氏锥虫感染后存活的4个基因座Tbbr1-4（布氏锥虫反应1-4）。Tbbr1（3号染色体）和Tbbr2（12号染色体）具有独立作用，Tbbr3（7号染色体）和Tbbr4（19号染色体）通过基因间相互作用检测。Tbbr2精确定位到一个2.15 Mb的片段，包含26个基因。
Trypanosoma brucei brucei infects livestock, with severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to this parasite. However, no genes controlling these differences were mapped. We studied the genetic control of survival after T. b. brucei infection using recombinant congenic (RC) strains, which have a high mapping power. Each RC strain of BALB/c-c-STS/A (CcS/Dem) series contains a different random subset of 12.5% genes from the parental “donor” strain STS/A and 87.5% genes from the “background” strain BALB/c. Although BALB/c and STS/A mice are similarly susceptible to T. b. brucei, the RC strain CcS-11 is more susceptible than either of them. We analyzed genetics of survival in T. b. brucei-infected F2 hybrids between BALB/c and CcS-11. CcS-11 strain carries STS-derived segments on eight chromosomes. They were genotyped in the F2 hybrid mice and their linkage with survival was tested by analysis of variance. We mapped four Tbbr (Trypanosoma brucei brucei response) loci that influence survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have effects on survival independent of inter-genic interactions (main effects). Tbbr3 (chromosome 7) influences survival in interaction with Tbbr4 (chromosome 19). Tbbr2 is located on a segment 2.15 Mb short that contains only 26 genes. This study presents the first identification of chromosomal loci controlling susceptibility to T. b. brucei infection. While mapping in F2 hybrids of inbred strains usually has a precision of 40–80 Mb, in RC strains we mapped Tbbr2 to a 2.15 Mb segment containing only 26 genes, which will enable an effective search for the candidate gene. Definition of susceptibility genes will improve the understanding of pathways and genetic diversity underlying the disease and may result in new strategies to overcome the active subversion of the immune system by T. b. brucei. Trypanosoma brucei are extracellular protozoa transmitted to mammalian host by the tsetse fly. They developed several mechanisms that subvert host's immune defenses. Therefore analysis of genes affecting host's resistance to infection can reveal critical aspects of host-parasite interactions. Trypanosoma brucei brucei infects many animal species including livestock, with particularly severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to T. b. brucei. However, genes controlling susceptibility to this parasite have not been mapped. We analyzed the genetic control of survival after T. b. brucei infection using CcS/Dem recombinant congenic (RC) strains, each of which contains a different random set of 12.5% genes of their donor parental strain STS/A on the BALB/c genetic background. The RC strain CcS-11 is even more susceptible to parasites than BALB/c or STS/A. In F2 hybrids between BALB/c and CcS-11 we detected and mapped four loci, Tbbr1-4 (Trypanosoma brucei brucei response 1–4), that control survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have independent effects, Tbbr3 (chromosome 7) and Tbbr4 (chromosome 19) were detected by their mutual inter-genic interaction. Tbbr2 was precision mapped to a segment of 2.15 Mb that contains 26 genes.
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影响因子：
3.2
作者：
DEMANT, P;HART, AAM
通讯作者：
HART, AAM
DOI：
10.1073/pnas.1232392100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Hanotte, O;Ronin, Y;Teale, A
通讯作者：
Teale, A
影响因子：
5
作者：
Graefe, SEB;Meyer, BS;Fleischer, B
通讯作者：
Fleischer, B
影响因子：
3.8
作者：
Goodhead, Ian;Archibald, Alan;Noyes, Harry A.
通讯作者：
Noyes, Harry A.
影响因子：
5
作者：
Badalová, J;Svobodová, M;Lipoldová, M
通讯作者：
Lipoldová, M