title: Mice deficient in the putative phospholipid flippase ATP11C exhibit altered erythrocyte shape, anemia, and reduced erythrocyte life span.
abstract: Transmembrane lipid transporters are believed to establish and maintain phospholipid asymmetry in biological membranes; however, little is known about the in vivo function of the specific transporters involved. Here, we report that developing erythrocytes from mice lacking the putative phosphatidylserine flippase ATP11C showed a lower rate of PS translocation in vitro compared with erythrocytes from wild-type littermates. Furthermore, the mutant mice had an elevated percentage of phosphatidylserine-exposing mature erythrocytes in the periphery. Although erythrocyte development in ATP11C-deficient mice was normal, the mature erythrocytes had an abnormal shape (stomatocytosis), and the life span of mature erythrocytes was shortened relative to that in control littermates, resulting in anemia in the mutant mice. Thus, our findings uncover an essential role for ATP11C in erythrocyte morphology and survival and provide a new candidate for the rare inherited blood disorder stomatocytosis with uncompensated anemia.
authors.affiliation: From the Ramaciotti Immunization Genomics Laboratory and.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yabas
authors.affiliation: Cancer and Vascular Biology Group, Department of Immunology, The John Curtin School of Medical Research, and the Clinical Haematology Unit, The Canberra Hospital, Canberra, Australian Capital Territory 2605, Australia.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Coupland
authors.affiliation: the Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia, and.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cromer
authors.affiliation: the Division of Biomedical Science and Biochemistry, Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Winterberg
authors.affiliation: the Liver Research Group, Australian National University Medical School at the Canberra Hospital, Canberra, Australian Capital Territory 2605, Australia.
authors.forename: Narci C
authors.initials: NC
authors.lastname: Teoh
authors.affiliation: the Clinical Haematology Unit, The Canberra Hospital, Canberra, Australian Capital Territory 2605, Australia.
authors.forename: James
authors.initials: J
authors.lastname: D'Rozario
authors.affiliation: the Division of Biomedical Science and Biochemistry, Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Kiaran
authors.initials: K
authors.lastname: Kirk
authors.affiliation: the Division of Biomedical Science and Biochemistry, Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.affiliation: Cancer and Vascular Biology Group, Department of Immunology, The John Curtin School of Medical Research, and.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Parish
authors.affiliation: From the Ramaciotti Immunization Genomics Laboratory and anselm.enders@anu.edu.au.
authors.forename: Anselm
authors.initials: A
authors.lastname: Enders
mesh_terms: D000137:Acid-Base Imbalance / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001693:Biological Transport, Active; D002470:Cell Survival / Q000502:physiology; D004910:Erythrocyte Membrane / Q000201:enzymology* / Q000235:genetics; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D000251:Adenosine Triphosphatases
keywords: ATP11C; Anemia; Erythrocyte; Flippase; Lipid Transport; P4 ATPases; Phosphatidylserine; Phospholipid; Plasma Membrane; Stomatocytosis