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High-throughput sleep phenotyping produces robust and heritable traits in Diversity Outbred mice and their founder strains

BT. Keenan, RJ. Galante, J. Lian, P. Simecek, DM. Gatti, L. Zhang, DC. Lim, KL. Svenson, GA. Churchill, AI. Pack

. 2020 ; 43 (5) : . [pub] 20200512

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural

Perzistentní odkaz   https://www.medvik.cz/link/bmc21020556

Grantová podpora
R01 GM070683 NIGMS NIH HHS - United States
R01 HL111725 NHLBI NIH HHS - United States
P01 HL094307 NHLBI NIH HHS - United States

E-zdroje Online Plný text

NLK Free Medical Journals od 1978 do Před 6 měsíci
ProQuest Central od 2016-10-01 do Před 1 rokem
Health & Medicine (ProQuest) od 2016-10-01 do Před 1 rokem
Psychology Database (ProQuest) od 2016-10-01 do Před 1 rokem

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Citace poskytuje Crossref.org

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