Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Max Planck Institute of Psychiatry, Munich, Germany.
J Sleep Res. 2018 Aug;27(4):e12557. doi: 10.1111/jsr.12557. Epub 2017 Jul 11.
Meis homeobox 1 (Meis1) is a transcription factor functioning in the development of the nervous system and the cardiovascular system. Both common and rare variants within the gene have been associated with restless legs syndrome (RLS), while its association with symptoms of insomnia has also been discovered recently. RLS is associated with sleep disturbances, and while Meis1 haploinsufficiency is one of the most promising strategies for an RLS animal model, sleep phenotyping of Meis1 knockout mice has never been conducted. We report a detailed sleep analysis of heterozygous Meis1 knockout mice and challenge it with pramipexole, a dopamine agonist used in the treatment of RLS. At baseline, the Meis1-haploinsufficient mice had a trend towards lower delta power in the electroencephalogram (EEG) during sleep compared to the wild-type littermates, possibly indicating reduced sleep quality, but not sleep fragmentation. Pramipexole had a sleep disrupting effect in both genotype groups. In addition, it exerted differential effects on the EEG power spectra of the two mouse lines, remarkably elevating the theta power of the mutant mice during recovery more than that of the wild-types. In conclusion, Meis1 haploinsufficiency seems to have only a modest effect on sleep, but the gene may interact with the sleep-disrupting effect of dopamine agonists.
Meis 同源盒 1（Meis1）是一种转录因子，在神经系统和心血管系统的发育中发挥作用。该基因的常见和罕见变异都与不安腿综合征（RLS）有关，而其与失眠症状的关联最近也被发现。RLS 与睡眠障碍有关，虽然 Meis1 半合子不足是 RLS 动物模型最有前途的策略之一，但 Meis1 敲除小鼠的睡眠表型分析从未进行过。我们报告了杂合 Meis1 敲除小鼠的详细睡眠分析，并对其进行了普拉克索（一种用于治疗 RLS 的多巴胺激动剂）挑战。在基线时，与野生型同窝仔相比，Meis1-半合子不足的小鼠在睡眠期间脑电图（EEG）中的 delta 功率有降低的趋势，这可能表明睡眠质量降低，但不包括睡眠碎片化。普拉克索在两种基因型小鼠中均具有破坏睡眠的作用。此外，它对两种小鼠品系的脑电图功率谱产生了不同的影响，在恢复期间显著提高了突变型小鼠的 theta 功率，而野生型小鼠的提高幅度更大。总之，Meis1 半合子不足似乎对睡眠只有适度的影响，但该基因可能与多巴胺激动剂的睡眠破坏作用相互作用。
