Deficient heme and globin synthesis in embryonic stem cells lacking the erythroid-specific δ-aminolevulinate synthase gene

Hideo Harigae, Naruyoshi Suwabe, Peter H. Weinstock, Mayumi Nagai, Hiroyoshi Fujita, Masayuki Yamamoto, Shigeru Sassa

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

The erythroid-specific isoform of δ-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) calls 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 calls were increased similarly both in the wild-type end mutant cells. In contrast, heme content, the number of benzidine-positive cells, adult globin protein, and mRNA for β-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 call differentiation, which involves hemoglobin synthesis.

Original languageEnglish
Pages (from-to)798-805
Number of pages8
JournalBlood
Volume91
Issue number3
DOIs
Publication statusPublished - 1998 Feb 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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