Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation

作者：Yamamoto Masatatsu; Arimura Hiroshi; Fukushige Tomoko; Minami Kentarou; Nishizawa Yukihiko; Tanimoto Akihide; Kanekura Takuro; Nakagawa Masayuki; Akiyama Shin ichi; Furukawa Tatsuhiko^*

来源：Molecular and Cellular Biology, 2014, 34(6): 1077-1084.

DOI：10.1128/MCB.00865-13

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.

• 出版日期2014-3