Disruption of retinoid-related orphan receptor β changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice
Disruption of retinoid-related orphan receptor β changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice
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DOI：
10.1093/emboj/17.14.3867
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发表时间：
1998-07-15
期刊：
影响因子：
11.4
通讯作者：
Becker-André, M
中科院分区：
文献类型：
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作者：
André, E;Conquet, F;Becker-André, M
孤儿核受体ROR β在参与感觉信息处理的中枢神经系统区域中表达，包括脊髓、丘脑和感觉小脑皮质。此外，ROR β定位于哺乳动物计时系统的三个主要解剖学组成部分，视交叉上核、视网膜和松果体。ROR β mRNA水平在视网膜酸性松果体中以昼夜节律振荡，该昼夜节律在恒定黑暗中持续存在，ROR β（-/-）小鼠表现出鸭子般的步态，短暂的雄性不能进行性繁殖，以及遭受出生后变性的严重紊乱的视网膜。因此，成年ROR β（-/-）小鼠是盲的，但它们的昼夜活动节律仍然受到光-暗循环的影响。有趣的是，在恒定黑暗的条件下，ROR β（-/-）小鼠显示出延长的自由奔跑节律性。ROR β（-/-）小鼠的总体行为表型，连同ROR β基因的染色体定位，表明与40年前描述的自发性小鼠突变vacillans密切相关。
The orphan nuclear receptor ROR beta is expressed in areas of the central nervous system which are involved in the processing of sensory information, including spinal cord, thalamus and sensory cerebellar cortices, Additionally, ROR beta localizes to the three principal anatomical components of the mammalian timing system, the suprachiasmatic nuclei, the retina and the pineal gland. ROR beta mRNA levels oscillate in retina acid pineal gland with a circadian rhythm that persists in constant darkness, ROR beta(-/-) mice display a ducklike gait, transient male incapability to sexually reproduce, and a severely disorganized retina that suffers from postnatal degeneration. Consequently, adult ROR beta(-/-) mice are blind, yet their circadian activity rhythm is still entrained by light-dark cycles, Interestingly, under conditions of constant darkness, ROR beta(-/-) mice display an extended period of free-running rhythmicity, The overall behavioral phenotype of ROR beta(-/-) mice, together with the chromosomal localization of the ROR beta gene, suggests a close relationship to the spontaneous mouse mutation vacillans described > 40 years ago.