2005 Fiscal Year Final Research Report Summary
Regulation of host defense and development by innate-immunity signal transduction system
| Project/Area Number |
15380201
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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 | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Hokkaido University (2004-2005)
Iwate University (2003) |
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Principal Investigator |
MORIMATSU Masami Hokkaido University, Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (70241370)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yoshio Iwate University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (10252123)
YOSHIMATSU Kumiko Hokkaido University, Graduate School of Medicine, Instructor, 大学院・医学研究科, 助手 (90220722)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Innate immunity / NF-kappaB / LPS / Inflammation / Embryonic lethality / Dermatitis / Allergy |
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| Research Abstract |
In innate immune system, specific pattern molecules such as LPS bind to Toll-like receptors and activate signal transduction pathway involving NF-kappaB. Recently we identified a novel nuclear IkB molecule, MAIL. In this study we focused on MAIL and other NF-kappaB related molecules.
1. Analysis of MAIL deficient mice
Embryonic lethality was observed for about 90% of MAIL deficient mice. Hypoplasia of the liver was suggested to be a possible cause for this embryonic lethality. Remaining 10% of MAIL deficient mice were born alive. These mice developed severe atopic dermatitis-like disease.
2. Analysis of transcriptional regulation of the MAIL gene
We cloned LPS-reactive upstream region of the mouse MAIL gene, and analyzed its promoter function by using a series of mutated sequences. An NF-kappaB binding site located at -229 to -220 bp was revealed to be an essential target of MAIL expression. Overexpression of MAIL protein suppressed the LPS-induced promoter activity of the MAIL gene. These data indicate that MAIL expression is upregulated by NF-kappaB, and it is controlled, at least in part, by an autoregulation mechanism.
3. Analysis of an NF-kappaB target gene product, BRCA2
BRCA2, an NF-kappaB target molecule, plays essential roles for cell growth and embryogenesis through its DNA repair and recombination function. We demonstrated that BRCA2 proteins from the mouse and dog interact with Rad51 recombinase. We found a novel insertion/deletion polymorphism in canine BRCA2, which is located in a nuclear localization signal. This polymorphism was associated with nuclear localization efficiency and mammary tumor morbidity.
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Research Products
(12 results)
