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

Hortle, E; Nijagal, B; Bauer, DC; Jensen, LM; Ahn, SB; Cockburn, IA; Lampkin, S; Tull, D; McConville, MJ; McMorran, BJ; Foote, SJ; Burgio, G

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

Hortle, E

Nijagal, B Bauer, DC Jensen, LM Ahn, SB Cockburn, IA Lampkin, S Tull, D McConville, MJ McMorran, BJ Foote, SJ Burgio, G

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Publisher:: AMER SOC HEMATOLOGY
Publication Type:: Journal Article
Citation:: Blood, 2016, 128, (9), pp. 1290-1301
Issue Date:: 2016-09-01

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Field	Value	Language
dc.contributor.author	Hortle, E https://orcid.org/0000-0001-9633-5638
dc.contributor.author	Nijagal, B
dc.contributor.author	Bauer, DC
dc.contributor.author	Jensen, LM
dc.contributor.author	Ahn, SB
dc.contributor.author	Cockburn, IA
dc.contributor.author	Lampkin, S
dc.contributor.author	Tull, D
dc.contributor.author	McConville, MJ
dc.contributor.author	McMorran, BJ
dc.contributor.author	Foote, SJ
dc.contributor.author	Burgio, G
dc.date.accessioned	2022-08-10T03:15:51Z
dc.date.available	2016-07-14
dc.date.available	2022-08-10T03:15:51Z
dc.date.issued	2016-09-01
dc.identifier.citation	Blood, 2016, 128, (9), pp. 1290-1301
dc.identifier.issn	0006-4971
dc.identifier.issn	1528-0020
dc.identifier.uri	http://hdl.handle.net/10453/159840
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER SOC HEMATOLOGY
dc.relation.ispartof	Blood
dc.relation.isbasedon	10.1182/blood-2015-09-666834
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine
dc.subject.classification	Immunology
dc.subject.mesh	AMP Deaminase
dc.subject.mesh	Animals
dc.subject.mesh	Cellular Senescence
dc.subject.mesh	Erythrocytes
dc.subject.mesh	Erythropoiesis
dc.subject.mesh	Ethylnitrosourea
dc.subject.mesh	Half-Life
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Malaria
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Mutation
dc.subject.mesh	Plasmodium chabaudi
dc.subject.mesh	Erythrocytes
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Plasmodium chabaudi
dc.subject.mesh	Malaria
dc.subject.mesh	Ethylnitrosourea
dc.subject.mesh	AMP Deaminase
dc.subject.mesh	Erythropoiesis
dc.subject.mesh	Mutation
dc.subject.mesh	Half-Life
dc.subject.mesh	Male
dc.subject.mesh	Immunity, Innate
dc.subject.mesh	Cellular Senescence
dc.title	Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice.
dc.type	Journal Article
utslib.citation.volume	128
utslib.location.activity	United States
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1103 Clinical Sciences
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
dc.date.updated	2022-08-10T03:15:49Z
pubs.issue	9
pubs.publication-status	Published
pubs.volume	128
utslib.citation.issue	9

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.

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http://hdl.handle.net/10453/159840