| First Author | Nakajima O | Year | 1999 |
| Journal | EMBO J | Volume | 18 |
| Issue | 22 | Pages | 6282-9 |
| PubMed ID | 10562540 | Mgi Jnum | J:58508 |
| Mgi Id | MGI:1347738 | Doi | 10.1093/emboj/18.22.6282 |
| Citation | Nakajima O, et al. (1999) Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. EMBO J 18(22):6282-9 |
| abstractText | Erythroid 5-aminolevulinate synthase (ALAS-E) catalyzes the first step of heme biosynthesis in erythroid cells. Mutation of human ALAS-E causes the disorder X-linked sideroblastic anemia. To examine the roles of heme during hematopoiesis, we disrupted the mouse ALAS-E gene. ALAS-E-null embryos showed no hemoglobinized cells and died by embryonic day 11.5, indicating that ALAS-E is the principal isozyme contributing to erythroid heme biosynthesis. In the ALAS-E-null mutant embryos, erythroid differentiation was arrested, and an abnormal hematopoietic cell fraction emerged that accumulated a large amount of iron diffusely in the cytoplasm. In contrast, we found typical ring sideroblasts that accumulated iron mostly in mitochondria in adult mice chimeric for ALAS-E-null mutant cells, indicating that the mode of iron accumulation caused by the lack of ALAS-E is different in primitive and definitive erythroid cells. These results demonstrate that ALAS-E, and hence heme supply, is necessary for differentiation and iron metabolism of erythroid cells. |
