| Project/Area Number |
13670435
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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 |
Legal medicine
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| Research Institution | Jichi Medical School |
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Principal Investigator |
IWAMOTO Sadahiko Jichi Medical School, Dept.of Medicine, Assos.Professor, 医学部, 助教授 (10232711)
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| Co-Investigator(Kenkyū-buntansha) |
KUMADA Maki Jichi Medical School, Dept.of Medicine, Assist.Professor, 医学部, 助手 (40326830)
OKUDA Hiroshi Jichi Medical School, Dept.of Medicine, Assos.Professor, 医学部, 助教授 (50285772)
KAMESAKI Toyomi Jichi Medical School, Dept.of Medicine, Lecturer, 医学部, 助手 (90316513)
KAJII Eiji Jichi Medical School, Dept.of Medicine, Professor, 医学部, 教授 (40204391)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | rat ABO homologue / paralogous gene / ABH antigen expression / transgenic rat / ラットABOオーソログ |
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| Research Abstract |
Histo-blood group ABH antigens are important not only for blood transfusion but also for organ transplantation. To improve the clinical management of transplantation, development of ABO-mismatched animal models is desirable. Rats are more suitable for ordinary examination of organ transplantation because of the larger body size compared with mice. To evaluate the availability of rats as an animal model, we studied rat ABO homologue and established human A- and B-transferase transgenic rats. A DNA fragment corresponding to exon 7 of the human ABO gene was amplified from Wistar rat genomic DNA and sequenced. Using the amplified fragments as a probe for Southern blotting, multiple hybridized bands appeared on both EcoRI and BamHI digested genomes of seven rat strains, which showed variations in the band numbers among the strains. Four cDNAs were cloned from a Wistar rat, three of which showed A-transferase activity and one of which showed B-transferase activity. These activities were dependent on the equivalent residues at 266 and 268 of human ABO transferase. Wild Wistar rats expressed A-antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen was not stained in any organs studied, while a transcript from the ABO homologue with B-transferase activity was ubiquitous. Human A-transferase and B-transferase were transferred into Wistar rats. A-transgenic rats expressed A-antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas, and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs as A-transgenic rats. If the hominoid ABO ancestral genes consisted of multicopy genes with A and B transferase activity like rats, they must donate or accept gene fragments from each other and may produce a locus composed of A-alleles and B-alleles. This estimation must be resolved by further genome projects in rats and other mammals.
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