title: The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrow.
abstract: B lymphopoiesis begins in the fetal liver, switching after birth to the bone marrow, where it persists for life. The unique developmental outcomes of each phase are well documented, yet their molecular requirements are not. Here we describe two allelic X-linked mutations in mice that caused cell-intrinsic arrest of adult B lymphopoiesis. Mutant fetal liver progenitors generated B cells in situ but not in irradiated adult bone marrow, which emphasizes a necessity for the affected pathway only in the context of adult bone marrow. The causative mutations were ascribed to Atp11c, which encodes a P4-type ATPase with no previously described function. Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development.
authors.affiliation: Department of Genetics, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Siggs
authors.forename: Carrie N
authors.initials: CN
authors.lastname: Arnold
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Elaine
authors.initials: E
authors.lastname: Pirie
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Nemazee
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology
chemical_list: C489921:Ebf1 protein, mouse; D007075:Immunoglobulin M; D015851:Interleukin-7; D015534:Trans-Activators; D012313:RNA; C000605549:ATP11C protein, mouse; D000251:Adenosine Triphosphatases