Role of heterozygous and homozygous alleles in cryptochrome-deficient mice
Role of heterozygous and homozygous alleles in cryptochrome-deficient mice
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DOI：
10.1016/j.neulet.2021.136415
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发表时间：
2022-01-10
影响因子：
2.5
通讯作者：
Nakamura, Wataru
中科院分区：
文献类型：
--
作者：
Oda, Yoshiaki;Takasu, Nana N.;Nakamura, Wataru
生理和行为的昼夜节律基于细胞水平的分子系统，受时钟基因调节，包括隐花色素基因、Cry1 和 Cry2。在哺乳动物中，下丘脑视交叉上核 (SCN) 中的昼夜节律起搏器维持整个身体的昼夜节律。 Cry1 和 Cry2 在调节昼夜节律方面发挥着不同的作用。然而，操纵时钟基因对杂合和纯合等位基因 Cry1 和 Cry2 的不同影响仍不清楚。因此，本研究旨在了解隐花色素基因在调节昼夜节律系统中的单倍性。我们检查了小鼠 SCN 切片和垂体外植体中的轮跑活动节律和 PER2::LUC 表达节律。与野生型小鼠相比，Cry1(-/-)或Cry2(-/-)小鼠的自由奔跑行为节律以及SCN和垂体中PER2::LUC表达的周期缩短或延长。 Cry1(+/-) 小鼠的昼夜节律与野生型小鼠相似，但 Cry2(+/-) 小鼠的周期更长。 Cry1(-/-) 小鼠中 PER2::LUC 表达的幅度表现出更快的阻尼。因此，Cry1缺乏会影响昼夜节律周期的长度和昼夜节律系统的稳定性。 Cry2 缺陷的单个等位基因会影响昼夜节律，而 Cry1 缺陷的单个等位基因会得到补偿。
The circadian rhythms of physiology and behavior are based on molecular systems at the cellular level, which are regulated by clock genes, including cryptochrome genes, Cry1 and Cry2. In mammals, the circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus maintains the circadian rhythms throughout the body. Cry1 and Cry2 play distinct roles in regulating the circadian rhythm. However, the different effects of manipulating clock genes in heterozygous and homozygous alleles, Cry1 and Cry2, remain unclear. Therefore, this study aimed to understand the haplosufficiency of cryptochrome genes in regulating the circadian system. We examined wheel-running activity rhythms and PER2::LUC expression rhythms in SCN slices and pituitary explants in mice. Compared with wild-type mice, Cry1(-/-) or Cry2(-/-) mice had shortened or lengthened periods in free-running behavioral rhythms and PER2::LUC expression in the SCN and pituitary gland. Cry1(+/-) mice had similar circadian rhythms as wild-type mice, although Cry2(+/-) mice had lengthened periods. The amplitude of PER2::LUC expression exhibited faster damping in Cry1(-/-) mice. Therefore, Cry1 deficiency affects the circadian period length and stability of the circadian system. A single allele of Cry2 deficiency affects the circadian rhythm, whereas that of Cry1 deficit is compensated.