title: Abcb10 role in heme biosynthesis in vivo: Abcb10 knockout in mice causes anemia with protoporphyrin IX and iron accumulation.
abstract: Abcb10, member 10 of the ABC transporter family, is reportedly a part of a complex in the mitochondrial inner membrane with mitoferrin-1 (Slc25a37) and ferrochelatase (Fech) and is responsible for heme biosynthesis in utero. However, it is unclear whether loss of Abcb10 causes pathological changes in adult mice. Here, we show that Abcb10(-/-) mice lack heme biosynthesis and erythropoiesis abilities and die in midgestation. Moreover, we generated Abcb10(F/-); Mx1-Cre mice, with Abcb10 in hematopoietic cells deleted, which showed accumulation of protoporphyrin IX and maturation arrest in reticulocytes. Electron microscopy images of Abcb10(-/-) hematopoietic cells showed a marked increase of iron deposits at the mitochondria. These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia.
authors.affiliation: Department of Molecular Oncology, Graduate School Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masatatsu
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukushige
authors.forename: Kentarou
authors.initials: K
authors.lastname: Minami
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000740:Anemia / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D041905:Erythroid Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics; D006418:Heme / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D011524:Protoporphyrins / Q000235:genetics / Q000378:metabolism*; D012156:Reticulocytes / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; C410734:Abcb10 protein, mouse; D011524:Protoporphyrins; D006418:Heme; C028025:protoporphyrin IX; D007501:Iron