scholarly journals A novel ENU-induced ankyrin-1 mutation impairs parasite invasion and increases erythrocyte clearance during malaria infection in mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hong Ming Huang ◽  
Denis C. Bauer ◽  
Patrick M. Lelliott ◽  
Andreas Greth ◽  
Brendan J. McMorran ◽  
...  

2016 ◽  
Author(s):  
Hong Ming Huang ◽  
Denis C. Bauer ◽  
Patrick M. Lelliott ◽  
Andreas Greth ◽  
Brendan J. McMorran ◽  
...  

AbstractGenetic 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 malariaPlasmodium chabaudiinfection. Parasites inAnk-1(MRI61689/+)erythrocytes grew normally, but red cells showed resistance to merozoite invasion. UninfectedAnk-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 ofAnk-1(MRI61689/+)erythrocytes. This paper highlights the complex roles ankyrin plays in mediating malaria resistance.



1981 ◽  
Vol 46 (02) ◽  
pp. 547-549 ◽  
Author(s):  
E M Essien ◽  
M I Ebhota

SummaryDuring acute malaria infection, platelets in human platelet-rich plasma are hypersensitive to the addition of ADP between 1.0 uM and 5.0 uM, or adrenaline 0.11 uM as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 uM), 39.8 ± 27 (1SD), was significantly greater than the value in 6 controls (5.2±6.7 (1SD); t = 3, 51 P <0.005). A similar pattern of response was obtained with higher ADP concentrations (2.4,4.5 or 5.0 uM) in 22 patients and 20 control subjects (89.9±14.9% vs 77.8±16.5% (1SD) t = 2.45, P <0.02). Addition of 4.5 uM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls.Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 ± 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2±15.7 ng/ml; t = 13.44, P <0.002).



2006 ◽  
Vol 2 (4) ◽  
pp. 331-344 ◽  
Author(s):  
Jenny Miu ◽  
Andrew Mitchell ◽  
Helen Ball ◽  
Nicholas Hunt
Keyword(s):  


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