Expression of haPer1 and haBmal1 in Syrian hamsters:: Heterogeneity of transcripts and oscillations in the periphery
Expression of haPer1 and haBmal1 in Syrian hamsters:: Heterogeneity of transcripts and oscillations in the periphery
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DOI：
10.1177/0748730403262871
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发表时间：
2004-04-01
影响因子：
3.5
通讯作者：
Bittman, EL
中科院分区：
文献类型：
--
作者：
Tong, YH;Guo, HN;Bittman, EL
昼夜节律的分子生物学已在小鼠中进行了广泛的研究，并且在该物种中已充分确定了规范生物钟基因在外周器官中的广泛表达。相比之下，尽管叙利亚仓鼠广泛用于昼夜节律组织和光周期反应的研究，但有关 haPer1、haPer2 和 haBmal1 外周表达的信息却少得多。此外，对小鼠睾丸中这些基因的振荡表达的检查产生了不一致的结果，并且对 haPer1 和 haBmal1 的性腺表达或其环境控制知之甚少。为了解决这些问题，作者检查了暴露于 DD 的仓鼠心脏、肾脏、肝脏、肌肉、脾脏和睾丸中 haPer1 和 haBmal1 的模式。在大多数器官中，Northern 印迹表明每种信使 RNA (mRNA) 均存在单个转录本。 haPer1 在主观白天晚些时候达到峰值，haBmal1 在主观夜间达到峰值。然而，对 SCN 和肌肉 haPer1 的仔细检查发现，存在两个大小相似的主要转录本，以及 3'-非翻译区域中不同的次要转录本。在仓鼠睾丸中，发现了两个 haPer1 转录本，这两个转录本相对于相应的小鼠转录本均被截短，并且都包含与 mPer1 内含子 18 同源的序列。两个睾丸转录本都不包含核定位信号，并且 haPer1 转录本缺乏推定的 C 端 CRY1 结合域。此外，睾丸偏离了一般模式，因为 haPer1 和 haBmal1 均在主观夜间达到峰值。原位杂交显示，haPer1（而非 haBmal1）在生精小管中表现出异质分布。仓鼠睾丸也表达 2 haPer2 转录本，但没有明显的昼夜节律变化。在第二个实验中，发现长期暴露于足以诱导性腺退化的 DD 可以消除两个睾丸 haPer1 转录本的昼夜节律振荡。相比之下，性腺退化伴随着 haBmal1 更强劲的节律。
The molecular biology of circadian rhythms has been extensively studied in mice, and the widespread expression of canonical circadian clock genes in peripheral organs is well established in this species. In contrast, much less information about the peripheral expression of haPer1, haPer2, and haBmal1 is available in Syrian hamsters despite the fact that this species is widely used for studies of circadian organization and photoperiodic responses. Furthermore, examination of oscillating expression of these genes in mouse testis has generated discrepant results, and little is known about gonadal expression of haPer1 and haBmal1 or their environmental control. To address these questions, the authors examined the pattern of haPer1 and haBmal1 in heart, kidney, liver, muscle, spleen, and testis of hamsters exposed to DD. In most organs, Northern blots suggested the existence of single transcripts of each of these messenger RNAs (mRNAs). haPer1 peaked in late subjective day and haBmal1 during the late subjective night. Closer inspection of SCN and muscle haPer1, however, revealed the existence of two major transcripts of similar size, as well as minor transcripts that varied in the 3'-untranslated region. In hamster testis, two haPer1 transcripts were found, both of which are truncated relative to the corresponding mouse transcript and both of which contain a sequence homologous to intron 18 of mPer1. Neither testis transcript contains a nuclear localization signal, and haPer1 transcripts lacked the putative C-terminal CRY1-binding domain. Furthermore, the testis deviated from the general pattern in that haPer1 and haBmal1 both peaked in the subjective night. In situ hybridization revealed that haPer1, but not haBmal1, showed a heterogeneous distribution among seminiferous tubules. Hamster testis also expresses 2 haPer2 transcripts, but no circadian variation is evident. In a second experiment, long-term exposure to DD sufficient to induce gonadal regression was found to eliminate circadian oscillations of both testicular haPer1 transcripts. In contrast, gonadal regression was accompanied by a more robust rhythm of haBmal1.