| Project/Area Number |
10558119
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory animal science
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| Research Institution | Chiba University |
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Principal Investigator |
TOKUHISA Takishi Chiba University Graduate School of Medicine, Developmental Genetics Professor, 大学院・医学研究科, 教授 (20134364)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Seiji Chiba University Graduate School of Medicine, Developmental Genetics, Assistant, 大学院・医学研究科, 助手 (50282455)
HATANO Masahiko Chiba University Graduate School of Medicine, Developmental Genetics, Associate Professor, 大学院・医学研究科, 助教授 (20208523)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1999: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1998: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Bcl6 / BAZF / Knockout mice / Transcriptional repressor / Apoptosis / Cardiac myocytes / 特発性心筋性 / モデルマウス / 心筋炎 / 好酸球 / IL-5 / 転写抑制活性 |
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| Research Abstract |
The Bcl6 gene encodes a sepuence-specific transcriptional repressor and is ubiquitously expressed in adult murine tissues including heart muscle. We have made Bcl6-deficient (Bcl6-/-) mice and histologically examined hearts from Bcl6-/-mice. Bcl6-/-mice displayed massive myocarditis with eosinophilic infiltration after 4-6 weeks of age. Since expression of the Bcl6 gene was induced in normal cardiac myocytes after 2 weeks of age and there after detected through adulthood, loss of Bcl16 in matue cardiac myocytes may be related with induction of myocarditis. In order to examine the relation, bone marrow cells from Bcl6-/-mice were adoptively transferred in sublethally irradiated RAG1-deficient mice. Although massive eosinophilic infiltration was detected in conjunctive and spleen from chimeric mice, no myocarditis was observed in the mice. Furthermore, electron microscopic analysis of cardiac myocytes from Bcl6-/-mice revealed a spectrum of degenerative changes prior to eosinophilic infiltration. Thus, Bcl6 may not be essential to maturation of cardiac myocytes but play a role in protection of mature cardiac myocytes from eosinophilic inflammation.
We have cloned a novel Bcl6 homologous gene (BAZF ; Bcl6 associated zinc finger protein). The predicted amino acid sequence of BAZF indicated that the BTB/POZ domain and the five repeats of the Kruppel-like zinc finger motif locate in the NH2-terminal region and the COOH-terminal region, respectively. BAZF could associate with Bcl6 at the BTB/POZ domain and localized in the nucleus. Since zinc-finger motifs of BAZF were 94% identical to those of Bcl6 at the amino acid level, BAZF bound specifically to the DNA binding sequence of Bcl6 and functiond as a transcriptional repressor. Expression of BAZF mRNA is detected in heart and lung. Therefore, the biochemicl character of BAZF is similar to that of Bcl6 although the tissue expression pattern of BAZF differs from that of Bcl6.
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