2001 Fiscal Year Final Research Report Summary
Analysis for gene function of the XPG gene using Xpg-kockout mice.
| Project/Area Number |
12680820
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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 |
Laboratory animal science
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
HARADA Yoshinobu National Institute of Radiological Sciences, Frontier Research Center, Researcher, フロンティア研究センター, 研究員 (90192707)
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| Co-Investigator(Kenkyū-buntansha) |
SUN Xue zhi National Institute of Radiological Sciences, Environmental and Toxicological Sciences Research Group, Researcher, 比較環境研究グループ, 研究員 (00284323)
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| Project Period (FY) |
2000 – 2001
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| Keywords | xeroderma pigmentosum group G / knock-out mice / DNA excision repair / cerebrum / cerebellum / calbodin-D28 |
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| Research Abstract |
Laboratory mice carrying the nonfunctional xeroderma pigmentosum group G gene (the mouse counterpart of the human XPG gene) alleles have been generated by using gene-targeting and embryonic stem cell technology. Homozygote animals of this autosomal recessive disease exhibited signs and symptoms, such as postnatal growth retardation, reduced levels of activity, progressive ataxia and premature death, similar to the clinical manifestations of Cockayne syndrome(CS). Histological analysis of the cerebellum revealed multiple pyknotic cells in the Purkinje cell layer of the xpg homozygotes, which had atrophic cell bodies and shrunken nuclei. Further examination by an immunohistochemistry for calbindin-D 28k (CaBP) showed that a large number of immunoreactive Purkinje cells were atrophic and their dendritic trees were smaller and shorter than in wild-type littermates. These results indicated a marked degeneration of Purkinje cells in the xpg mutant cerebellum. Study by in situ detection of DNA fragmentation in the cerebellar cortex demonstrated that some deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin in situ nick labeling (TUNEL)-positive cells appeared in the granule layer of the mutant mice, but few cell deaths were confirmed in the Purkinje layer. These results suggested Purkinje cell degeneration in the mutant cerebellum was underway, in which much Purkinje cell death had not appeared, and the appearance of some abnormal cerebellar symptoms in the xpg-deficient mice was not only due to a marked Purkinje cell degeneration, but also to damage of other cells.
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Research Products
(2 results)
