Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice

Elinor Hortle, Brunda Nijagal, Denis C. Bauer, Lora M. Jensen, Seong Beom Ahn, Ian A. Cockburn, Shelley Lampkin, Dedreia L. Tull, Malcolm J. McConville, Brendan J. McMorran, Simon J. Foote, Gaetan Burgio

    Research output: Contribution to journalArticlepeer-review

    23 Citations (Scopus)

    Abstract

    The factors that determine red blood cell (RBC) lifespan and the rate of RBC aging have not been fully elucidated. In several genetic conditions, including sickle cell disease, thalassemia, and G6PD deficiency, erythrocyte lifespan is significantly shortened. Many of these diseases are also associated with protection from severe malaria, suggesting a role for accelerated RBC senescence and clearance in malaria resistance. Here, we report a novel, N-ethyl-N-nitrosourea-induced mutation that causes a gain of function in adenosine 5'-monophosphate deaminase (AMPD3). Mice carrying the mutation exhibit rapid RBC turnover, with increased erythropoiesis, dramatically shortened RBC lifespan, and signs of increased RBC senescence/eryptosis, suggesting a key role for AMPD3 in determining RBC half-life. Mice were also found to be resistant to infection with the rodent malaria Plasmodium chabaudi. We propose that resistance to P. chabaudi is mediated by increased RBC turnover and higher rates of erythropoiesis during infection.

    Original languageEnglish
    Pages (from-to)1290-1301
    Number of pages12
    JournalBlood
    Volume128
    Issue number9
    DOIs
    Publication statusPublished - 1 Sep 2016

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