In vivo selection for Leishmania donovani miniexon genes that increase virulence in Leishmania major †

In vivo selection for Leishmania donovani miniexon genes that increase virulence in Leishmania major †
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增加利什曼原虫毒力的杜氏利什曼原虫小外显子基因的体内选择 †

DOI:
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发表时间:
2004
影响因子:
3.6
通讯作者:
G. Matlashewski
G. Matlashewski
中科院分区:
生物学2区
文献类型:
--
作者:
Wen;G. Matlashewski

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不同种类的利什曼原虫导致与利什曼病相关的多种病理,包括导致致命性内脏感染的杜氏利什曼原虫和导致非致命性皮肤感染的大型利什曼原虫。在试图确定这些相关的旧大陆利什曼原虫物种之间的基因型差异,这有助于他们独特的表型特征,我们已经引入了一个L。donovani粘粒文库转化到L.主要选择L。donovani序列,这可能会增加L. BALB/c小鼠的主要毒力。通过这种方法,我们已经确定了一个区域的L。donovani基因组,其在内脏和皮肤部位的毒力增加,并且与L.主要基因组当这些L. donovani序列重新导入L.主要是增强了L.主要,增加其在内脏和皮肤部位的存活能力。感染水平增加的区域被确定为来自L. donovani。脉冲场电泳结果表明,L. donovani在几个染色体位置含有miniexon基因序列,而L. major,其仅在2号染色体中含有miniexon基因序列。由于锥虫中前mRNA成熟需要小外显子衍生的转录物,该观察结果表明小外显子基因表达的增加与毒力增加相关。随着利什曼原虫基因组序列的可用,本文所述的体内选择程序将有助于鉴定负责与利什曼原虫感染相关的不同致病性表型的其他种属特异性序列。
Different species of Leishmania are responsible for the diverse pathologies associated with leishmaniasis including Leishmania donovani which results in fatal visceral infection and Leishmania major which causes non‐fatal cutaneous infection. In an attempt to identify genotypic differences between these related Old World Leishmania species which contribute to their distinct phenotypic characteristics, we have introduced a L. donovani cosmid library into L. major to select for L. donovani sequences which may increase L. major virulence in BALB/c mice. Through this approach, we have identified a region of the L. donovani genome which increased virulence in both visceral and cutaneous sites and was divergent from the corresponding region of the L. major genome. When these L. donovani sequences were reintroduced into L. major, they enhanced the overall virulence of L. major, increasing its ability to survive in both visceral and cutaneous sites. The region responsible for increased infection levels was determined to be the miniexon gene array derived from chromosome 36 of L. donovani. Pulse field electrophoresis revealed that L. donovani contained miniexon gene sequences in several chromosome locations as opposed to L. major which contains miniexon gene sequences only in chromosome 2. Because of the requirement for miniexon‐derived transcripts in maturation of pre‐mRNAs in trypanosomatids, this observation suggests that the increased expression of miniexon genes is associated with increased virulence. As the genome sequence for Leishmania becomes available, the in vivo selection procedure described within will be useful to identify additional species‐specific sequences responsible for different pathogenic phenotypes associated with Leishmania infection.
重大利什曼原虫 2 号染色体的结构改变作为二倍体的证据,包括迷你外显子阵列的自发扩增。
DOI: 10.1016/0166-6851(89)90009-1
发表时间: 1989
影响因子: 1.5
作者:
Iovannisci,DM;Beverley,SM
通讯作者: Beverley,SM
在几种蜥蜴利什曼原虫物种中发现了两种不同的功能性剪接前导 RNA 基因阵列。
DOI: 10.1016/s0020-7519(02)00131-5
发表时间: 2002
影响因子: 4
作者:
Yu,MichaelC;Orlando,TCristina;Sturm,NancyR;Zhou,Liang;Saito,RMako;Floeter-Winter,LucileM;Campbell,DavidA
通讯作者: Campbell,DavidA
五种利什曼原虫的分子核型及基因位置和染色体重排分析。
DOI: 10.1016/0166-6851(87)90092-2
发表时间: 1987
影响因子: 1.5
作者:
Samaras,N;Spithill,TW
通讯作者: Spithill,TW