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A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait
by
Hirano, Arisa
, Lin, Shu-Ting
, Hsu, Pei-Ken
, Fu, Ying-Hui
, Sakai, Noriaki
, Jones, Christopher R.
, Saigoh, Kazumasa
, Okuro, Masashi
, Saigoh, Noriko
, Kaasik, Krista
, McMahon, Thomas
, Yamazaki, Maya
, Nishino, Seiji
, Xu, Ying
, Ptáček, Louis J.
, Zhang, Luoying
in
Affect - physiology
/ Aged
/ Amino Acid Sequence
/ Animals
/ Biological Sciences
/ Circadian Clocks - genetics
/ Circadian rhythm
/ Circadian rhythms
/ Emotions
/ Female
/ Genetics
/ Genotype & phenotype
/ Humans
/ Male
/ Mental depression
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Middle Aged
/ Molecular Sequence Data
/ Period Circadian Proteins - genetics
/ Period Circadian Proteins - metabolism
/ Photoperiod
/ PNAS Plus
/ Protein Stability
/ Proteins
/ Rodents
/ Seasonal Affective Disorder - genetics
/ Seasonal variations
/ Seasons
/ Sleep
/ Sleep Disorders, Circadian Rhythm - genetics
/ Transgenic animals
2016
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A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait
by
Hirano, Arisa
, Lin, Shu-Ting
, Hsu, Pei-Ken
, Fu, Ying-Hui
, Sakai, Noriaki
, Jones, Christopher R.
, Saigoh, Kazumasa
, Okuro, Masashi
, Saigoh, Noriko
, Kaasik, Krista
, McMahon, Thomas
, Yamazaki, Maya
, Nishino, Seiji
, Xu, Ying
, Ptáček, Louis J.
, Zhang, Luoying
in
Affect - physiology
/ Aged
/ Amino Acid Sequence
/ Animals
/ Biological Sciences
/ Circadian Clocks - genetics
/ Circadian rhythm
/ Circadian rhythms
/ Emotions
/ Female
/ Genetics
/ Genotype & phenotype
/ Humans
/ Male
/ Mental depression
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Middle Aged
/ Molecular Sequence Data
/ Period Circadian Proteins - genetics
/ Period Circadian Proteins - metabolism
/ Photoperiod
/ PNAS Plus
/ Protein Stability
/ Proteins
/ Rodents
/ Seasonal Affective Disorder - genetics
/ Seasonal variations
/ Seasons
/ Sleep
/ Sleep Disorders, Circadian Rhythm - genetics
/ Transgenic animals
2016
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A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait
by
Hirano, Arisa
, Lin, Shu-Ting
, Hsu, Pei-Ken
, Fu, Ying-Hui
, Sakai, Noriaki
, Jones, Christopher R.
, Saigoh, Kazumasa
, Okuro, Masashi
, Saigoh, Noriko
, Kaasik, Krista
, McMahon, Thomas
, Yamazaki, Maya
, Nishino, Seiji
, Xu, Ying
, Ptáček, Louis J.
, Zhang, Luoying
in
Affect - physiology
/ Aged
/ Amino Acid Sequence
/ Animals
/ Biological Sciences
/ Circadian Clocks - genetics
/ Circadian rhythm
/ Circadian rhythms
/ Emotions
/ Female
/ Genetics
/ Genotype & phenotype
/ Humans
/ Male
/ Mental depression
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Middle Aged
/ Molecular Sequence Data
/ Period Circadian Proteins - genetics
/ Period Circadian Proteins - metabolism
/ Photoperiod
/ PNAS Plus
/ Protein Stability
/ Proteins
/ Rodents
/ Seasonal Affective Disorder - genetics
/ Seasonal variations
/ Seasons
/ Sleep
/ Sleep Disorders, Circadian Rhythm - genetics
/ Transgenic animals
2016
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A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait
Journal Article
A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait
2016
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Overview
In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes.
Publisher
National Academy of Sciences
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