2003 Fiscal Year Final Research Report Summary
Identification of a chromosomal region that is responsible for memory T cell homeostasis in a mutant mouse.
| Project/Area Number |
14570275
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
MURAKAMI Masaaki Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00250514)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Memory / T cells / B cells / mutant mouse / 血小板増多 |
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| Research Abstract |
It is well known that memory T cells proliferate faster and react to the pathogens stronger compared to naive T cells. I found a female mutant mouse carrying excess amount of memory T cells of both CD4+ and CD8+ in a SPF colony in National Jewish Medical Center, Denver, CO. The phenotype is inherited as an autosomal recessive manor. Thymus size is small (about 10% of controls) and the numbers of double positive cells reduces dramatically. T cell differentiation is partially but dominantly blocked at a step where preTCR signaling is necessary named DN3. Platelets significantly increased in serum and this result is consistent with excess amount of megakaryocytes in spleen. In addition, the number of immature B cells decreased significantly and differentiation of B cells is blocked at large preB stage where preBCR signaling is important. I performed bone marrow transplantation experiment to analyze if the mutation in lymphoid progenitor is or if it in microenvironment is necessary for the phenotype of T and B cells in the mutant mice. The mutation in lymphoid progenitor cells themselves is necessary to see the phenotype. In order to identify a DNA fragment carrying a responsible gene that induces the phenotype in the mutant mice, we employed SSPL method. We crossed B10#4 mice with NZB mice to get F2 mice and got over 100 phenotype + and -offspring. We identified 1cM DNA fragment in chromosome #2 that is responsible for the mutant and the fragment has about 40 genes according to NCBI database. Result of RT-PCR experiment for a gene in the fragment was fascinating, since splicing pattern of the gene is different between the B10#4 and control mice. I analyzed sequence of the gene and found that there were two mutations in the introns of the gene.
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Research Products
(24 results)
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[Publications] S.Chiba, H.Okamoto, S.Kon, C.Kimura, M.Murakami, M.Inobe, Y.Matsui, T.Sugawara, T.Shimizu, T.Uede, A.Kitabatake: "Development of atherosclerosis in osteopontin transgenic mice."Heart and vessels.. 16. 111-117 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] M.Nomura, K.Yamashita, M.Murakami, M.Takehara, H.Echizenya, M.Sunahara, N.Kitagawa, M.Fujita, H.Furukawa, T.Uede, S.Todo: "Induction of donor-specific tolerance by adenovirus mediated CD4OIg gene therapy in rat liver transplantation."Transplantation.. 1403-1410 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kanaya K, Tsuchida Y, Inobe M, Murakami M, Hirose T, Kon S, Kawaguchi S, Wada T, Yamashita T, Ishii S, Uede T.: "Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD4OIg prolongs survival of composite tissue allografts in rat model."Transplantation.. 75. 275-281 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Tosa N, Murakami M, Jia WY, Yokoyama M, Masunaga T, Iwabuchi C, Inobe M, Iwabuchi K, Miyazaki T, Onoe K, Iwata M, Uede T.: "Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis."Int Immunol.. 15. 741-749 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Yasukawa H, Ohishi M, Mon H, Murakami M, Chinen T, Aki D, Hanada T, Takeda K, Akira S, Hoshijima M, Hirano T, Chien KR, Yoshimura A.: "IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages."Nat Immunol.. 4. 551-556 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamashita K, Masunaga T, Yanagida N, Takehara M, Hashimoto T, Kobayashi T, Echizenya H, Hua N, Fujita M, Murakami M, Funikawa H, Uede T, Todo S.: "Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD4OIg plus CTLA4Ig gene therapies."Transplantation.. 15. 1089-1196 (2003)
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「研究成果報告書概要(欧文)」より
