生物钟基因与疾病

生物钟的特征
自发性 (Self generated) ：并非正好24小时/周期 同步 (Circadian Entrainment)
Phase control Period control
Mouse activity entrains to light
12h light:12h dark 24 h dark 10 min light
N Huang et al. Science 2012;337:189-194
Mutations that reduce repression of CLOCK:BMAL1 transactivation by CRY localize to CLOCK PAS-B HI loop.
Published by AAAS
Bmal1 Clock
BMAL CLOCK
PER CRY
Wild Type
Period Cryptochrome
Clock Mutants
Bmal Knockouts
Vitaterna et al., Science 94; McDearmon et al., Science 06
E-boxes (5′-CACGTG-3′) E′-boxes(5′-CACGTT-3′)
Lipids Health Dis. 2010; 9: 22.
Daily profiles of expression of clock genes Bmal1, Cry1, Per2 and Rev-erbα in the mouse heart at the postnatal day 1 (P1), P3, P5.
• WelshFig05video.mov
Ron Konopka
Wild type Clock+/Clock-/-
生物钟基因Clock突变小鼠
JOSEPH TAKAHASHI Science. 29, 1994; 264(5159): 719–725
Circadian Clock Manipulations: Activity
N Huang et al. Science 2012;337:189-194
| | | NATURE REVIEWS NEUROSCIENCE VOLUME 4 AUGUST 2003 649
睡眠障碍与生物钟
Daily profiles of expression of clock genes Bmal1, Cry1, Per2 and Re源自文库-erbα in the mouse SCN at the postnatal day 1 (P1), P3, P5.
Explaining shift lag and jet lag
The mammalian circadian timing system
Hypothalamus
Retino-hypothalamic tract
The paired suprachiasmatic nuclei (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals.
10 mins of light per day are sufficient to reset the clock
Clock in the Brain
Overwhelming evidence indicates that the suprachiasmatic nucleus (SCN), a paired structure located in the anterior hypo-thalamus contains a circadian pacemaker.
Published by AAAS
N Huang et al. Science 2012;337:189-194
N Huang et al. Science 2012;337:189-194
Published by AAAS
N Huang et al. Science 2012;337:189-194
Fergal C et al. Cancer Letters, Volume 342, Issue 1, 2014, 9 - 18
Cell. 1997, 16; 89(4): 641–653
Shimomura et al. eLife 2013;2:e00426.
basic helix-loop-helix PER-ARNTSIM (bHLH-PAS)
Lipids Health Dis. 2010; 9: 22.
Bedont JL, Blackshaw. Front Syst Neurosci. 2015 May 8;9:74
Age-related Changes in Sleep Pattern
MELATONIN
NIGHT
Annals of Medicine, 2014; 46: 208–220
Circadian rhythms are abolished with complete lesions of the SCN.
SCN transplants into the third ventricle and hypothalamus restores rhythmicity in previously arrhythmic animals.
生物钟基因与疾病 Circadian genes and diseases
Circadian Rhythm of Sleep
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2
3
4
Days
The term "circadian", was coined by Franz Halberg
The term circadian comes from two Latin words namely “circa” means around “diem/dies” means day Circadian means “approximately one day’’