| Project/Area Number |
62480441
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
HIAI Hiroshi Laboratory of Experimental Pathology, Aichi Cancer Center Research Inst.Chief, 病理学第二部, 部長 (10073131)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIZUKA Yasuaki Aichi Cancer Center Research Institute Emeritus Director, 名誉所長 (60073095)
武馬 裕美子 愛知県がんセンター, 研究所・病理学第二部, 技師
BUMA Yumiko Laboratory of Experimental Pathology, Aichi Cancer Center Research Inst.Research
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1988: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1987: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | SL Mice / Virus-host interaction / endogenous retrovirus / maternal resistant factor / epigenetic control of gene expression / モノクローナル抗体 / 母系担抗因子 / SL / Niマウス / 内在性白血病ウイルス / 母系抵抗因子 |
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| Research Abstract |
The SL-Ni mouse, a substrain of the SL strain developed in Japan as a lymphomaprone strain, has been studied as a model of autoimmunity based on abnormal virus-host interaction, since they develop necrotizing arteritis and glomerulonephritis associated with expression of endogenous murine leukemia veruses (MuLVs). The expression of endogenous MuLV in this strain is found polymorphic and it is inhibited epigenetically and type-specifically by a naternal resistance factor (MRF) transmitted via milk. We isolated two sublines of SL/Ni mice: SL/Ni-Eco- lacks MuLV expression by MRF and SL/Ni-Eco+ expresses MuLV but without MRF. We also studied virology, genetics and immunobiology of all SL substrains to verify their interrelationship. Fractionation of SL/Ni-Eco- serum by salt fractionation, absorption chromatography and gel filtration revealed the MRF activity is co-chromatographed with 7S immunoglobulin containing anti MuLV antibody as revealed by passive hemadsorption (PHA) or by indirect immunofluorescence antibody technique. This antibody reacted broadly with ecotropic MuLVs and exhibited variable cross reactivity with MCF and Moloney virus, but without virus neutralizing activity. All the supernatants of 10 hybridomas, prepared by fusion of SL/Ni-Eco- spleen cells and NS-1 cells and by screening with PHA, contained anti-MuLV gp70 antibodies (8 were IgM, one IgG2a and one IgG3) and their reactivity were similar to SL/Ni-Eco- serum. However, on bioassay, none of them effectively inhibited the expression of endogenous MuLV and inhibited lymphoma development in high virus strains. It has remained obscure whether the anti-MuLV antibody producing clones with biological activity are rarely detected by our screening procedure or they may have specific isotype such as IgA. Under the assumption of the nature of MRF is a species of anti-MuLV antibody, further study is indicated to elucidate molecular basis of endogenous virus expression.
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