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Deficient Heme and Globin Synthesis in Embryonic Stem Cells
Lacking the Erythroid-Specific  -Aminolevulinate Synthase Gene
Hideo Harigae,
Naruyoshi Suwabe,
Peter H. Weinstock,
Mayumi Nagai,
Hiroyoshi Fujita,
Masayuki Yamamoto, and
Shigeru Sassa
From The Rockefeller University, New York, NY; the Departments of
Biochemistry and Molecular Biology and Applied Physiology, Tohoku
University School of Medicine, Sendai, Japan; and the Center for
Tsukuba Advanced Research Alliance and Institute for Basic Medical
Sciences, University of Tsukuba, Tsukuba, Japan.
The erythroid-specific isoform of  -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  -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.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 798-805
© 1998 by The American Society of Hematology.
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