2005 Fiscal Year Final Research Report Summary
Oncogenesis of retrovirus induced-glioma and the development of animal model
| Project/Area Number |
15380207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
OCHIAI Kenji Hokkaido University, Graduate School of Veterinary Medicine, Associate Professor, 大学院獣医学研究科, 助教授 (80214162)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Kazuhiko Hokkaido University, Graduate School of Veterinary Medicine, Associate Professor, 大学院獣医学研究科, 助教授 (90250498)
ONO Etsuro Tottori University, Department of Agriculture, Professor, 農学部, 教授 (00160903)
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| Project Period (FY) |
2003 – 2005
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| Keywords | avian leukosis virus (ALV) / astrocytoma / oncogenesis / fowl / glioma / nervous system / transgenic mice |
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| Research Abstract |
The cause and pathological features of so-called fowl glioma (astrocytoma) had not been determined. We have suggested that the cause is a subgroup A of avian leukosis virus (ALV). The subject of this research project is to clarify the pathogenicity of fowl glioma-inducing virus (FGV) and to analyze the molecular biological role of env gene and LTR in the neuropathogenicity. At first, chickens experimentally infected with FGV were pathologically examined. Whereas other isolated ALVs generally induce hematopoietic neoplasms, FGV was likely to replicate especially in brain and heart and induced nonsuppurative encephalitis and myocarditis, perineurioma, cerebellar hypoplasia as well as astrocytoma in nervous system. Genome sequence analysis suggested FGV to be combined with several virus strains. The U3 region of the LTR had a few deletions and several point mutations compared to that of other ALVs (EMBL, GenBank, and DDBJ nucleotide sequence databases under the accession number AB112960). The promoter activity of LTR also showed subtle differences, which may be related to the induction of glial neoplasm. In addition, histopathology of the 51 affected brains suggested the presence of a histological variant composed of diffuse proliferation of astrocytes and indicated that the disease entity should be named "retrovirus-induced astrocytoma" of chickens. To examine the promoter activity of FGV LTR in vivo, 13 lines of transgenic mice expressing a transgene under the control of the LTR promoter were generated and the tissue specificity of the expression was analyzed by monitoring mRNA in each line using the reverse transcription-polymerase chain reaction. The results indicated that the FGV LTR promoter was capable of driving a stable transgene expression especially in the central nervous system and testis although the LTR acted as a panspecific promoter in vivo.
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