Tissue-specific disruption of rhythmic expression of Dec1 and Dec2 in Clock mutant mice
Tissue-specific disruption of rhythmic expression of Dec1 and Dec2 in Clock mutant mice
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DOI：
10.1177/0748730405280195
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发表时间：
2005-10-01
影响因子：
3.5
通讯作者：
Kato, Y
中科院分区：
文献类型：
--
作者：
Noshiro, M;Furukawa, M;Kato, Y
DEC1和Dec2 -基本螺旋环-螺旋转录因子-在视交叉上核和其他外周组织中表现出昼夜节律表达，似乎通过抑制CLOCK/ bmal1激活的Per1、DEC1和Dec2启动子来调节哺乳动物的昼夜节律。作者提供了野生型和纯合型Clock突变小鼠（Clock/Clock）不同组织中Dec1、Dec2、Per2、Dbp和Npas2 mRNA表达模式的数据。Clock突变导致Dec1在肾脏、心脏和骨骼肌中的表达极度减少，但在肝脏中没有，而在肝脏、肾脏和心脏中强烈抑制Dec2的表达，而在骨骼肌中Dec2的表达保持节律性。Per2也显示了Clock突变对节律性的组织依赖性破坏，而在Clock突变小鼠中，Dbp的节律性表达在所有检查的组织中都消失了。Npas2是与Clock在结构和功能上相关的基因，在肝脏和肾脏中表达水平显著，具有较强的节律性，也受到Clock突变的影响。由于Clock突变，Dec1和Dec2的表达以及外周Per2、Dbp和Npas2的表达发生了显著变化，这表明在大多数组织中，Clock在这些基因的表达中起主要作用。然而，在Clock突变小鼠的肝脏和肾脏中Dec1的昼夜节律表达以及骨骼肌中Dec2的昼夜节律表达表明，某些组织中存在不依赖于Clock的昼夜节律调节。
DEC1 and DEC2-basic helix-loop-helix transcription factors-exhibit a circadian expression in the suprachiasmatic nucleus and other peripheral tissues and seem to play roles in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoters of Per1, Dec1, and Dec2. The authors present data on the expression patterns of mRNA for Dec1, Dec2, Per2, Dbp, and Npas2 in various tissues of wild-type and homozygous Clock mutant mice (Clock/Clock). The Clock mutation resulted in extreme reduction of Dec1 expression in kidney, heart, and skeletal muscle but not in liver, whereas it strongly repressed Dec2 expression in liver, kidney, and heart, while Dec2 expression in skeletal muscle remained rhythmic. Per2 also showed the tissue-dependent disruption of the rhythmicity by Clock mutation, whereas rhythmic expression of Dbp in Clock mutant mice disappeared in all tissues examined. Npas2, a structurally and functionally related gene to Clock, showed significant levels of expression in the liver and kidney with a robust rhythmicity, which was also affected by Clock mutation. These marked changes in the Dec1 and Dec2 expression, as well as in the Per2, Dbp, and Npas2 expression in the periphery by Clock mutation, indicated that CLOCK plays a major role in the expression of these genes in most tissues. However, circadian expression of Dec1 in liver and kidney and that of Dec2 in skeletal muscle of Clock mutant mice suggested that CLOCK-independent circadian regulation operates in some tissues.