| First Author | Harigae H | Year | 1998 |
| Journal | Blood | Volume | 91 |
| Issue | 3 | Pages | 798-805 |
| PubMed ID | 9446639 | Mgi Jnum | J:116367 |
| Mgi Id | MGI:3694153 | Doi | 10.1182/blood.v91.3.798.798_798_805 |
| Citation | Harigae H, et al. (1998) Deficient heme and globin synthesis in embryonic stem cells lacking the erythroid-specific delta-aminolevulinate synthase gene. Blood 91(3):798-805 |
| abstractText | The erythroid-specific isoform of delta-aminolevulinate synthase (ALAS-E) catalyzes the first step of heme biosynthesis in erythroid cells, and ALAS-E gene mutations are known to be responsible for x-linked sideroblastic anemia. To study the role of ALAS-E in erythroid development, we prepared mouse embryonic stem (ES) cells carrying a disrupted ALAS-E gene and examined the effect of the lack of ALAS-E gene expression on erythroid differentiation. We found that mRNAs for erythroid transcription factors and TER119-positive cells were increased similarly both in the wild-type and mutant cells. In contrast, heme content, the number of benzidine-positive cells, adult globin protein, and mRNA for beta-major globin were significantly decreased in the mutant cells. These results were confirmed using another ES differentiation system in vitro and suggest that ALAS-E expression, hence heme supply, is critical for the late stage of erythroid cell differentiation, which involves hemoglobin synthesis. |
