| Project/Area Number |
10308036
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE |
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Principal Investigator |
YONEKAWA HIROMICHI THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, DEPARTMENT OF LABORATORY ANIMAL SCIENCE, ACTING HEAD(VICE DERECTOR OF THE INSTITUTE), 東京都臨床医学総合研究所・研究員(副所長) (30142110)
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| Co-Investigator(Kenkyū-buntansha) |
CHOJI TAYA TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, DEPARTMENT OF LABORATORY ANIMAL SCIENCE, INVESTIGATOR, 東京都臨床医学総合研究所, 研究員 (90175456)
OKAMATO MIEKO TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, DEPARTMENT OF LABORATORY ANIMAL SCIENCE, INVESTIGATOR, 東京都臨床医学総合研究所, 研究員 (80152354)
MAEDA YUKIKO TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, DEPARTMENT OF LABORATORY ANIMAL SCIENCE, SENIOR INVESTIGATOR, 東京都臨床医学総合研究所, 研究員 (40109947)
KARASUYAMA Hajime TOKYO MEDICAL DENTAL UNIVERCITY GRADUATE SCHOOL, DEPARTMENT OF IMMUNE REGULATION PROFESSOR, 医学研究科, 教授 (60195013)
KIKKAWA YOSHIAKI TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, DEPARTMENT OF LABORATORY ANIMAL SCIENCE, INVESTIGATOR, 東京都臨床医学総合研究所, 研究員 (20280787)
ISHIKAWA AKIRA NAGOYA UNIVERSITY GRADIATE SCHOOL OF BIOAGRICULTURAL SCIENCES ASSOCIATED PROFESSOR (20211724)
WAKANA SHIGEHARU RIKEN GENOMIC SCIENCES CENTER, INVESTIGATOR (90192434)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥33,480,000 (Direct Cost: ¥31,500,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2001: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2000: ¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1999: ¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1998: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | Model mouse for human diseases / Atopic dermatitis / Mice / NC / Nga / Radiation hybrid panel / Linkage disequilibrium / Microsatellite / MSM / Ms / アトピー性疾患 / 遺伝子マッピング / マウス / ヒト疾患モデル / 皮膚炎 / アレルギー |
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| Research Abstract |
NC/Nga (NC) is a newly discovered model mouse for human atopic dermatitis, NG mice showing specific symptoms such as dermatitis and overproduction of IgE. To detect the loci responsible for the onset of dermatitis in the mice, backcross (N_<2>) progeny between (NCxMSM/MS)F_<1> and NC were generated, where MSM/MS is an inbred strain from Japanese wild mice, Mus musculus molossinus, Linkage disequilibrium between dermatitis and various chromosome-specific microsatellite markers was then examined in the N2 segregants with severe dermatitis. The analysis revealed that the locus of the major determinant (designated here as derml) was tightly linked to D9Mit163, D9Mit72, D9Mit143, D9Mit103, D9Mit207, and D9Mit209, because these markers showed the highest and most significant ・_<2> values. Since no recombination was observed among the markers in our linkage map, a radiation hybrid (RH) panel was applied to locate the derml locus more precisely. The markers were separated on the RH map, and their order was D9Mit163--D9Mit72--D9Mit143--D9Mit103-- D9Mit207-- D9Mit209 from the centromere. Several functional candidate genes are located near the locus derml. These candidates are Thy1, Cd3d, Cd3e, Cd3g, Il10ra, Il18, and Csk, all of which could be involved in allergic responses through effects on T-cell function. Of these candidates, Csk is the strongest for NC dermatitis, since its map position was most tightly linked to the derml locus. We also generated three transgenic mouse strain which expressed allergen-specific IgE in blood. These transgenic mice will be applicable to disclose the mechanisms of atopic dermatitis.
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