Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA.
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Sleep. 2020 May 12;43(5). doi: 10.1093/sleep/zsz278.
This study describes high-throughput phenotyping strategies for sleep and circadian behavior in mice, including examinations of robustness, reliability, and heritability among Diversity Outbred (DO) mice and their eight founder strains.
We performed high-throughput sleep and circadian phenotyping in male mice from the DO population (n = 338) and their eight founder strains: A/J (n = 6), C57BL/6J (n = 14), 129S1/SvlmJ (n = 6), NOD/LtJ (n = 6), NZO/H1LtJ (n = 6), CAST/EiJ (n = 8), PWK/PhJ (n = 8), and WSB/EiJ (n = 6). Using infrared beam break systems, we defined sleep as at least 40 s of continuous inactivity and quantified sleep-wake amounts and bout characteristics. We developed assays to measure sleep latency in a new environment and during a modified Murine Multiple Sleep Latency Test, and estimated circadian period from wheel-running experiments. For each trait, broad-sense heritability (proportion of variability explained by all genetic factors) was derived in founder strains, while narrow-sense heritability (proportion of variability explained by additive genetic effects) was calculated in DO mice.
Phenotypes were robust to different inactivity durations to define sleep. Differences across founder strains and moderate/high broad-sense heritability were observed for most traits. There was large phenotypic variability among DO mice, and phenotypes were reliable, although estimates of heritability were lower than in founder mice. This likely reflects important nonadditive genetic effects.
A high-throughput phenotyping strategy in mice, based primarily on monitoring of activity patterns, provides reliable and heritable estimates of sleep and circadian traits. This approach is suitable for discovery analyses in DO mice, where genetic factors explain some proportion of phenotypic variation.
本研究描述了用于小鼠睡眠和昼夜节律行为的高通量表型策略，包括对多样性杂交（DO）小鼠及其八个亲本品系中的稳健性、可靠性和遗传性进行检验。
我们对 DO 群体（n=338）雄性小鼠及其八个亲本品系（A/J（n=6）、C57BL/6J（n=14）、129S1/SvlmJ（n=6）、NOD/LtJ（n=6）、NZO/H1LtJ（n=6）、CAST/EiJ（n=8）、PWK/PhJ（n=8）和 WSB/EiJ（n=6））进行了高通量睡眠和昼夜节律表型分析。我们使用红外光束中断系统将至少 40 秒的连续不活动定义为睡眠，并量化了睡眠-觉醒量和突发特征。我们开发了测定法来测量新环境中的睡眠潜伏期和改良的小鼠多睡眠潜伏期测试期间的睡眠潜伏期，并根据轮跑实验估算了昼夜节律周期。对于每个特征，在亲本品系中得出了广义遗传力（由所有遗传因素解释的变异性比例），而在 DO 小鼠中则计算了狭义遗传力（由加性遗传效应解释的变异性比例）。
表型对定义睡眠的不同不活动持续时间具有稳健性。在大多数特征中，都观察到了不同亲本品系之间的差异以及中等/高广义遗传力。DO 小鼠之间存在很大的表型变异性，表型是可靠的，尽管遗传力的估计值低于亲本小鼠。这可能反映了重要的非加性遗传效应。
基于对活动模式的监测，小鼠的高通量表型策略提供了睡眠和昼夜节律特征的可靠和遗传力估计。这种方法适用于 DO 小鼠的发现分析，其中遗传因素解释了部分表型变异。
