2003 Fiscal Year Final Research Report Summary
Regulation of Mast Cell Differentiation by mi Transcription Factor (MITE)
| Project/Area Number |
12002010
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
KITAMURA Yukihiko Osaka University, Graduate School of Frontier Biosciences, Professor, 生命機能研究科, 教授 (70028520)
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| Co-Investigator(Kenkyū-buntansha) |
JIPPO Tomoko Senri Kinran University, Faculty of Human Life Sciences, Lecture, 生活科学部, 講師 (70252658)
MORII Eiichi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10283772)
ITO Akihiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80273647)
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| Project Period (FY) |
2000 – 2003
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| Keywords | mutant mice / mast cell / c-kit receptor tyrosine kinase / MITF / hematopoietic stem cell / tissue environment |
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| Research Abstract |
We investigated the effect of MITF on development of mast cells. 1).Many mutant alleles have been reported in the mi locus that encodes MITF. We examined the interrelationship between the structure of mutant MITF and the biological effect of the mutated MITF. The mi is the firstly found mutant allele, and an arginine was deleted at the basic domain. The MITF produced by the mi mutant allele (mi-MITF) lacks DNA binding potential. Although the mi-MITF has no transcription ability, it can interact with other transcription factors and inhibit their functions (inhibitory mutation). The tg is a transgene insertion mutation, and MITF is not produced in cultured mast cells (CMCs) derived from tg/tg mice (null mutation). The phenotype of tg/tg CMCs was more severe than that of mi/mi CMCs. 2).The necessity of MITF for development of mast cells was examined by grafting bone marrow cells of normal (+/+) or tg/tg mice to irradiated W/Wv mice. W/Wv mice are deficient in mast cells due to the defect of multipotential hematopoietic stem cells. Erythrocytes, neutrophils, macrophages, B cells and T cells became of donor origin after the bone marrow transplantation from either +/+ or tg/tg mice. Mast cells developed in all examined tissues of W/Wv mice when +/+ bone marrow cells were injected, but did not when tg/tg bone marrow cells were injected. MITF appears essential for differentiation of mast cells from their precursors in tissues of adult mice.
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[Publications] Morii E, Ogihara H, Kim DK, Ito A, Oboki K, Lee YM, Jippo T, Nomura S, Maeyama K, Lamoreux ML, Kitamura Y: "Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi^<ce>/mi^<ce> mutant mice of which MITF lacks the zipper domain."Blood. 97. 2038-2044 (2001)
Description
「研究成果報告書概要(欧文)」より
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