Characterization of mice carrying multiple mutant genes which cause the different immunological defects.
| Project/Area Number |
03404068
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Kanazawa University |
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Principal Investigator |
HAYAKAWA Jun-ichiro Kanazawa Univ.School.of.Med., Prof., 医学部, 教授 (50110622)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGAKI Yasuto Kanazawa Univ.Faculty of Pharm.Sci, Research Asst., 薬学部, 教務職員 (20232275)
HASHIMOTO Noriyoshi Kanazawa Univ.School of Med., Instructor, 医学部, 助手 (50242524)
AKAO Nobuaki Kanazawa Univ.School of Med., Asst.Prof., 医学部, 講師 (00126559)
OHNO Shinsuke Kanazawa Univ, Cancer Res.Inst., Assoc.Prof., がん研究所, 助教授 (70019868)
NIKAIDO Osamu Kanazawa Univ.Faculty of Pharm.Sci., Prof., 薬学部, 教授 (60019669)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 1993: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1991: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | mouse / immunodeficient / beige / xid / carcinogenesis / UV irradiation / bone marrow / scid / 骨髄細胞 / 免疫不全 / 可移植性 / NK細胞 |
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| Research Abstract |
Multiple mutants strains, KSN-bg, KSN-xid, KSN-bg ; xid were bred from a nude strain, KSN.Each strain of mice has good reproduction performance and could be supplied for a small size experiment. Genetic profiles of these strains including microsatellite markers were identical so for examined loci, indicating these strains are congenic each other.. NK-cell activity of mice carrying beige gene, KSN-bg and KSN-bg ; xid was significantly reduced, although florescence-activated cell analysis of spleen cells indicated NK cells labeled with asialo-GM1 antibody were not decreased in mice with beige gene. This indicates that the reduced NK cell activity by beige mutation is due to the functional impairment of NK cells. The cell analysis also indicates that xid mutation induces the decrease in number of B cells in spleen and the amounts of IgG and IgM in serum. However, the comparison of the transplalntability of 7 human tumor cell lines in KSN,KSN-bg and KSN-xid mice, indicated no advantages in
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the double-mutant mice. The transplantability of human tumors in nude/bg/xid mice is now under investigation. These two kinds of double-mutant mice did not provide a model for human dirofilariasis. The SCID mice with beige mutation were also bred from the cross between C.B-17 SCID and KSN-bg mice. The introduction of beige mutation into SCID mice resulted in the significant reduction of NK cell activity and the transplantation of rat bone marrow experiments showed that SCID-bg mice take more easily than SCID mice, which result more severe Graft-versus-host reaction in the SCID-bg mice. In order to examine the surveillance effect of NK-cell activity in carcinogenesis, the tumor induction after UVB-irradiation were compared between KSN and KSN-bg mice at the daily doses of 160 and 320 J/m^2. At 160 J/m^2/day, significantly higher induction of skin tumor in KSN-bg mice than in KSN mice was observed, but at higher dose of 320 J/m^2/day higher induction was fouund in KSN mice. The results suggested that the role of NK-cell activity in UV-carcinogenesis, if any, is very marginal and after only very low dose of UVB-irradiation, Less
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Report
(4 results)
Research Products
(5 results)
