16 2 2004 4 Chinese Bulletin of Life Sciences Vol. 16, No. 2 Apr., 2004 1004-0374 (2004) 02-0104-05 1 100101 2 434025 9 24, Q41 A Advance in circadian rhythm genetics in mammals XU Zu-Yuan 1,2 (1 Beijing Genomics Institute, Institute of Genetics and Developmental Biology,Chinese Academy of Sciences, Beijing 100101, China; 2 College of Life Science, Yangtze University, Jingzhou 434025, China) Abstract: The circadian clock is a self-sustaining oscillator that has a period of about 24 hours and can synchronize itself to changing environmental conditionals to optimize an organisms performance. Besides their own regulation, clock genes can influence biochemical processes by modulating specific genes of biochemical pathways. Developments in the last few years using genetics and molecular biological tools have led to a new understanding of the molecular basis of the circadian clock in mammals. We review here these advances and the prospects for using the homologues as candidate genes in studies of human disorders in the circadian timing system. Key words: circadian rhythm; clock genes; entrainment; clock-controlled genes 24 (central clock) (SCN) 30 (entrainment) 10 2003-02-20 (1967 )
105 (CACGTG) [5] 1 ( ) 1.1 period 1971 Konopka [1] period (d) 1984 d period 1997 ( m, h) [2~4] period (m1 m3) iod E PER bhlh/pas E bhlh/pas m1 m3 [6~9] m1 mcry1 mrna SCN m1 mcry1 m3 m1 m1 m3 m3 -/- m1 mcry1 mrna m3 1.2 Cryptochrome Cry (mcry1 mcry2) SCN mcry1 RNA [10~13] mcry2 SCN m1 1 mcry1 mcry2 mcry1 -/- 24 mcry2 -/- 24 mcry1/mcry2 SCN m1 [12] mcry1 mcry2 mcry (mcry1 mcry2) -E mcry mper mper [13] 1.3 clock 1997 [14~15] 5 100kb 24 bhlh/pas( - - /PAS) 19 5' 3 A-T - 19 51 m E m - 19 m : m [16] 1.4 m (MOP3) [16~18] m SCN m1 mdbp (D ) m [18] CYCLE BMAL2(Mop9) 1.5 CK1ε 1988 [19] tau (CK1ε) [20~21] CK1ε ddbt PER PER NPAS2(MOP4) [22]
106 NPAS2 m1 mcry1 NPAS2 mrna dtim mtim 2 / CRY [23] bhlh-pas m1 m3 mcry1 mcry2 dclock m [15,18] mpers (mper1 mper2 mper3) mcrys (mcry1 mcry2) mper2 (mper1 mper3 ) mcrys / ms mcrys mper2 m [13] m1 mcry1 (M- ), mcry2 (E- ) M-E m1 [6] 3 (entrainment) ( ) 3.1 / CRYs [26] Ca 2+ 1 2 [24] mpers mpers CK1ε mcrys m, m mper2 mcry1 mcry2 m1 (m1 CT4~6 CT9~12) Daan [25] M-E ( ) SCN 1 2 Cry1 Cry2 Cry1/ Cry2 CREB MAP [27] 3.2 / 16 [29] Balsalobre [28]
107 37 [34] (retinoic acid) McNamara [30] RARα / Rev-erbα Rev-erbβ MOP4/ h1 Rev-erbα -6 camp CREB MAP DBP E4BP4 -α [31] 5 [32] Tau 4 (output pathways) [33] Panda 7 000 3 000 EST 650 (http://expression.gnf.org/circadian) [34] (DSPS) 24 - (ASPS) [35] 80~337 187~575 462 38 41~85 [33] ( 24 ) 2001 Toh [36] (ASPS) 4 19:30 4 30 24 h2 A-G CK1ε CK1ε hclock [37] 21~28 5%
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