HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakajima, O. Articles by Yamamoto, M. Search for Related Content PubMed PubMed Citation Articles by Nakajima, O. Articles by Yamamoto, M.

¹ Research Laboratory for Molecular Genetics, Yamagata University, Yamagata 990-9585, Japan
² Center for Tsukuba Advanced Research Alliance
³ Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8577, Japan
⁴ JST-ERATO Environmental Response Project, University of Tsukuba, Tsukuba 305-8577, Japan

Molecular defects in erythroid 5-aminolevulinate synthase (ALAS-E), the first enzyme in the heme biosynthetic pathway, cause X-linked sideroblastic anemia (XLSA). However, ring sideroblasts, the hallmark of XLSA, were not found in ALAS-E-deficient mouse embryos, indicating that simple ALAS-E-deficiency is not sufficient for ring sideroblast formation. To investigate the developmental stage-specific pathogenesis caused by heme-depletion, we attempted a complementation rescue of ALAS-E-deficiency. We exploited transgenic mouse lines expressing human ALAS-E at approximately half that of wild-type levels. In these hypomorphic embryos, most of the primitive erythroid cells were transformed into ring sideroblasts. The majority of the circulating definitive erythroid cells became siderocytes, enucleated erythrocytes containing iron deposits, and definitive ring sideroblasts were also observed. These iron-overloaded cells suffered from an /ß globin chain imbalance. Despite the iron overload, transferrin receptors were highly expressed in the erythroid cells, suggesting they contribute to the formation of ring sideroblasts and siderocytes. These results indicate that a partially depleted heme supply provokes ring sideroblast formation. The experimental generation of ring sideroblasts in animals would contribute to our understanding of the iron metabolism and its disorder in erythroid cells.

^* Correspondence: E-mail: masi{at}tara.tsukuba.ac.jp

This article has been cited by other articles:

				S. Okano, L. Zhou, T. Kusaka, K. Shibata, K. Shimizu, X. Gao, Y. Kikuchi, Y. Togashi, T. Hosoya, S. Takahashi, et al. Indispensable function for embryogenesis, expression and regulation of the nonspecific form of the 5-aminolevulinate synthase gene in mouse. Genes Cells, January 1, 2010; 15(1): 77 - 89. [Abstract] [Full Text] [PDF]

				A. Iolascon, L. De Falco, and C. Beaumont Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis Haematologica, March 1, 2009; 94(3): 395 - 408. [Abstract] [Full Text] [PDF]

				P. Cavadini, G. Biasiotto, M. Poli, S. Levi, R. Verardi, I. Zanella, M. Derosas, R. Ingrassia, M. Corrado, and P. Arosio RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload Blood, April 15, 2007; 109(8): 3552 - 3559. [Abstract] [Full Text] [PDF]

				S. Lyoumi, M. Abitbol, V. Andrieu, D. Henin, E. Robert, C. Schmitt, L. Gouya, H. de Verneuil, J.-C. Deybach, X. Montagutelli, et al. Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice Blood, January 15, 2007; 109(2): 811 - 818. [Abstract] [Full Text] [PDF]