| Project/Area Number |
10044231
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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 |
環境影響評価(含放射線生物学)
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| Research Institution | Tohoku University |
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Principal Investigator |
YASUI Akira Tohoku University, Institute of Development, Aging and Cancer, Department of Molecular Genetics, Professor, 加齢医学研究所, 教授 (60191110)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAO Masashi Tohoku University, Institute of Development, Aging and Cancer, Department of Molecular Genetics, Assistant Professor, 加齢医学研究所, 助手 (70216612)
岡村 均 神戸大学, 医学部, 教授 (60158813)
EKER A エラスムス大学, 医学部, 研究員
VAN der Hors エラスムス大学, 医学部, 研究員
BOOTSMA D. エラスムス大学, 医学部, 教授
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | DNA repair / gene targeting / repair deficient mouse / circadian rhythm / photo repair / 光回復酵素 / サーカディアンリズム / ノックアウトマウス / 活性酸素 / 老化 / ジーンターゲーティング / 青色光受容体 |
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| Research Abstract |
We isolated two mouse homologues of photolyase gene (mCry1 and mCry2), which encode proteins in the family of blue-light receptors. To explore the biological function of mammalian Cry1 and Cry2, we have generated cry1 and cry2 mutant mice through gene targeting in embryonic stem cells. Since these mutant mice are completely healthy and showed no overt phenotype, we analyzed the possible role for CRY proteins in the biological clock by measuring the circadian wheel-running behavior of cry-knockout mice under normal light/dark (LD) cycles and in constant darkness (DD). Since CRY proteins are able to function as blue-light receptor, these protein may be involved in the light entrainment ability. We found that mice lacking the Cry1 or Cry2 protein display accelerated and delayed free-running (DD) periodicity of locomotor activity, respectively. These findings suggest that Cry1 and Cry2 antagonistically modulate the period length of the clock. Above results indicate, however, that a deficiency in either gene does not produce a detectable loss of light entrainment of locomotor activity. Since cry1 mouse still contain a functional Cry2 protein, we generated double-mutant animals. To our surprise, in the absence of both proteins, an instantaneous and complete loss of free-running rhythmicity is observed. This suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhytjmicity.
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