Characterization of locomotor activity circadian rhythms in athymic nude mice.
Characterization of locomotor activity circadian rhythms in athymic nude mice.
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DOI：
10.1186/1740-3391-11-2
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发表时间：
2013-02-01
影响因子：
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通讯作者：
Golombek DA
中科院分区：
文献类型：
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作者：
Paladino N;Duhart JM;Mul Fedele ML;Golombek DA
在过去的十年中，昼夜节律失调与癌症发病率和进展之间的关系已经成为一个重要的话题。此外，基于时间药理学的治疗方法的使用也引起了人们的注意。由于胸腺发育失败而缺乏功能性T淋巴细胞，携带Foxn1（Δ/Δ）突变的小鼠（裸鼠）传统上被用于包括异种肿瘤植入在内的研究。由于免疫系统能够调节生物钟，我们研究了胸腺突变小鼠的昼夜节律系统是否有改变。记录2-4月龄Foxn1（Δ/Δ）小鼠（来自Swiss Webster背景）及其相应野生型（WT）对照的一般活动昼夜节律。分析了昼夜节律系统对不同操作（恒定黑暗、光脉冲和昼夜节律变化）的响应。胸腺小鼠和野生型小鼠的自由奔跑时间分别为23.86±0.03小时和23.88±0.05小时。两种菌株在主观夜早期施加10分钟或120分钟光脉冲后表现出相似的相位延迟，并且在昼夜节律时间（CT） 15光脉冲后，视交叉上核中表达c- fos的细胞数量没有差异。同样，两组在光-暗计划延迟6小时或提前6小时后重新同步所需的时间上没有显着差异。各组间的日活动比例、与授时数的相位角、主观夜持续时间等活动模式相似。由于胸腺Foxn1（Δ/Δ）小鼠在昼夜节律系统对实验操作的反应方面与WT对照组没有差异，我们得出结论，它们代表了一个很好的模型，可以将异种移植物植入与昼夜节律时间表的改变或时间药理学方法结合起来进行治疗。
The relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice. General activity circadian rhythms in 2–4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light–dark schedule) was analyzed. Free-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light–dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups. Since athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics.