Molecular analysis of mast cell activation in mouse models for autoinflammatory syndromes and its use for anti-inflammatory drug development
Project/Area Number |
25290036
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Laboratory animal science
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Research Institution | Tokai University |
Principal Investigator |
ABE Koichiro 東海大学, 医学部, 准教授 (90294123)
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Co-Investigator(Kenkyū-buntansha) |
RA Chisei 日本大学, 医学部, 客員教授 (60230851)
TAJIMA Atsushi 金沢大学, 医薬保健研究域, 教授 (10396864)
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Co-Investigator(Renkei-kenkyūsha) |
NUNOMURA Satoshi 佐賀大学, 医学部, 助教 (70424728)
KIMURA Minoru 東海大学, 医学部, 教授 (10146706)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
|
Keywords | 病態モデル / 関節炎 / 自然炎症 / 変異マウス / 疾患モデル / ミュータジェネシス / 遺伝学 / 実験動物学 / マウス遺伝学 / 疾患モデル動物 / ENUミュータジェネシス |
Outline of Final Research Achievements |
Autoinflammation syndromes are caused by an exaggerated innate immune system response without autoatibodies and selfreactive T cells, and the patients show spontaneous inflammation affecting multiple organs. The Ali14 and Ali18 are gain-of-function mutations in cell signaling effector enzyme genes, and trigger inflammation through the innate immune cells by unknown mechanisms. Because the double mutant with Ali18 and W/Wv , which lacks mast cell population, did not show autoinflammation, we analyzed cultured mast cells from mutant bone marrow.Ali14 and Ali18 mast cells showed lower calcium concentration for antigen stimulation. Further, micro-array analysis identified 1124 and 750 up-regulated genes specifically in Ali18 and Ali14 mast cells, respectively. Further, 127 genes were up-regulated in both mutant mast cells. Cell signaling pathways involving these up-regulated genes might provide insight into extensive repression against autoinflammation.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Disappearance of centroacinar cells in the Notch ligand-deficient pancreas.2015
Author(s)
Nakano Y, Negishi N, Gocho S, Mine T, Sakurai Y, Yazawa M, Abe K, Yagita H, Habu S, Kageyama R, Kawaguchi Y, Hozumi K.
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Journal Title
Genes to Cells
Volume: 33
Issue: 6
Pages: 500-511
DOI
Related Report
Peer Reviewed
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[Journal Article] Estrogen promotes Leydig cell engulfment by macrophages in male infertility.2014
Author(s)
Yu W, Zheng H, Lin W, Tajima A, Zhang Y, Zhang X, Zhang H, Wu J, Han D, Rahman NA, Korach KS, Gao GF, Inoue I, Li X.
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Journal Title
J Clin Invest
Volume: 124
Pages: 2709-2721
Related Report
Peer Reviewed
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