A novel ENU-induced ankyrin-1 mutation impairs parasite invasion and increases erythrocyte clearance during malaria infection in mice.
A novel ENU-induced ankyrin-1 mutation impairs parasite invasion and increases erythrocyte clearance during malaria infection in mice.
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一种新型的ENU诱导的Ankyrin-1突变会损害寄生虫的侵袭，并增加小鼠疟疾感染期间的红细胞清除率。
DOI：
10.1038/srep37197
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发表时间：
2016-11-16
影响因子：
4.6
通讯作者：
Burgio G
中科院分区：
文献类型：
--
作者：
Huang HM;Bauer DC;Lelliott PM;Greth A;McMorran BJ;Foote SJ;Burgio G
长期以来，人们一直认为各种红细胞（RBC）细胞骨架蛋白的遗传缺陷与疟疾感染易感性的变化有关。特别是，虽然锚蛋白（Ank-1）突变约占遗传性球形红细胞增多症（HS）病例的50%，但与疟疾的关联尚未得到证实，并且报告了相互矛盾的证据。我们描述了一种新的n -乙基-n -亚硝基脲（ENU）诱导的锚蛋白突变MRI61689，该突变产生两种不同的锚蛋白转录本：一种是引入剪接受体位点，导致移码，另一种是外显子跳过。Ank-1（MRI61689/+）小鼠表现出hs样表型，包括平均红细胞体积（MCV）减少，渗透脆弱性增加和红细胞变形性降低。它们还被发现对啮齿类疟疾（chabaudi Plasmodium）感染具有抗性。Ank-1（MRI61689/+）红细胞中的寄生虫生长正常，但红细胞对分裂子的侵袭表现出抗性。未感染的Ank-1（MRI61689/+）红细胞也更有可能在感染期间从循环中清除；“旁观者效应”。这种增加的清除率是一种新的耐药机制，在以前的锚蛋白小鼠模型中没有观察到。我们认为这种旁观者效应是由于Ank-1（MRI61689/+）红细胞的可变形性降低。本文重点介绍了锚定蛋白在调节疟疾耐药性中所起的复杂作用。
Genetic defects in various red blood cell (RBC) cytoskeletal proteins have been long associated with changes in susceptibility towards malaria infection. In particular, while ankyrin (Ank-1) mutations account for approximately 50% of hereditary spherocytosis (HS) cases, an association with malaria is not well-established, and conflicting evidence has been reported. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced ankyrin mutation MRI61689 that gives rise to two different ankyrin transcripts: one with an introduced splice acceptor site resulting a frameshift, the other with a skipped exon. Ank-1(MRI61689/+) mice exhibit an HS-like phenotype including reduction in mean corpuscular volume (MCV), increased osmotic fragility and reduced RBC deformability. They were also found to be resistant to rodent malaria Plasmodium chabaudi infection. Parasites in Ank-1(MRI61689/+) erythrocytes grew normally, but red cells showed resistance to merozoite invasion. Uninfected Ank-1(MRI61689/+) erythrocytes were also more likely to be cleared from circulation during infection; the “bystander effect”. This increased clearance is a novel resistance mechanism which was not observed in previous ankyrin mouse models. We propose that this bystander effect is due to reduced deformability of Ank-1(MRI61689/+) erythrocytes. This paper highlights the complex roles ankyrin plays in mediating malaria resistance.
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影响因子：
2.9
作者：
Grey JL;Kodippili GC;Simon K;Low PS
通讯作者：
Low PS
DOI：
10.4269/ajtmh.1997.57.507
发表时间：
1997-11-01
影响因子：
3.3
作者：
Dondorp, AM;Angus, BJ;Vreeken, J
通讯作者：
Vreeken, J
影响因子：
2.3
作者：
Gallagher, PG
通讯作者：
Gallagher, PG
影响因子：
20.3
作者：
Chishti, AH;Palek, J;Liu, SC
通讯作者：
Liu, SC
DOI：
10.1073/pnas.88.24.11022
发表时间：
1991-12-01
影响因子：
11.1
作者：
JAROLIM, P;PALEK, J;LIU, SC
通讯作者：
LIU, SC