産業技術総合研究所
生物機能工学研究部門
生物時計研究グループ
花井修次
| 時計遺伝子 Clock Genes | Allele アリル (Flyでは代表的なアリルのみ） |
変異源 Mutagen |
Class | 表現型 (free running under DD) | 文献 (M: mutant, G: gene isolation) | |
| Period | mouse Per1 | Per1tm1Brd(Per1Brdm1) | KO | 短周期 (-1.1h) Per2とWKOで無周期 |
M: Zheng2001 | |
| Per1tm1Drw (Per1ldc) | KO | Arrhythmic (無周期) | M: Bae2001 | |||
| Per1tm1Saco | KO | 短周期 | M: Cermakian2001 | |||
| mouse Per2 | Per2tm1Brd(Per2Brdm1) | KO | 短周期→無周期 発がん増加(Fu2002) |
M: Zheng1999 | ||
| Per2tm1Ccl | KO | 同上(tm1Brdと同じグループの別コンストラクト) | M: Fu2002 | |||
| Per2tm1Drw (Per2ldc) | KO | 無周期 | M: Bae2001 | |||
| Per2tm1Jt(Per2Luciferase) | KI | Per2のC末にLucを融合 行動は正常 |
M: Yoo2004 | |||
| mouse Per3 | Per3tm1Brd(Per3Brdm1) | KO | 短周期(0.5 h) | M: Shearman2000 | ||
| fly period | per01 (per0) (Q464@) | EMS | A, R | 無周期 | M: Konopka1971 G: Bargiello1984, Zehring1984, Reddy1984 |
|
| perL1 (perL) (V243D) | EMS | Hypo | 長周期 28-30 h | M: Konopka1971 | ||
| pers (perS) (S589N) | EMS | Hypo | 短周期 19 h | M: Konopka1971? | ||
| timeless | fly timeless | tim01 (tim0) | Δ2-3 | A, R | Arrhythmic | M: Sehgal1994 G: Myers1995 |
| timS1 | EMS | SD | Homo, 21.1 +/- 0.2 h; hetero, 22.2 +/- 0.1 | M: Rothenfluh2000Genetics | ||
| timL1 (K586M) | EMS | SD | Homo, 27.8; hetero, 25.5 | M: Rothenfluh-Hilfiker1995 G: Rothenfluh2000Genetics |
||
| timUL (E260K) | EMS | SD | Homo, 32.8; hetero, 25.6 | M: Rothenfluh-Hilfiker1997 G: Rothenfluh 2000Neuron |
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| Clock | mouse Clock | Clockm1Jt (Clockdelta19) | ENU | SD | 長周期、無周期 いわゆるClockマウス |
M: Vitaterna1994 G: King1997, Antoch1997 |
| Clocktm1.1Drw (Clockdelta5-6) | KO | A | 正常周期 Npas2とWKOで無周期 |
M, G: Debruyne2006 (Debruyne2007) |
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| fly Clk | ClkJrk (Q776@) |
EMS | SD | Homo, 無周期; hetero, 半数無周期 |
Allada1998 | |
| Clkar (Missense, exon 2/intron 2 splice site) | EMS |
A, R | Homo, 無周期; hetero, 正常 |
Allada2003 | ||
| Npas2 | mouse Npas2 | Npas2tm1Slm (NPAS-deltabHLH, NPAS2-lacZ) | KO | ? | 記憶、睡眠に異常 | Garcia2000 |
| Bmal | mouse Bmal1 | Arntltm1Bra | KO | A, R | Homo, 無周期; hetero, 正常 |
Bunger2000 |
| Arntltm1.1Weit | KO, conditinal | Homo+ubiquitous Cre, 無周期 | Storch2007 | |||
| mouse Bmal2 | NA | - | - | - | - | |
| fly cycle | cyc01 (A586T) | EMS | A, R | Homo, 無周期; hetero, 正常 |
Rutia1998 | |
| Cry | mouse Cry1 | Cry1tm1Jhjh | KO | A | 短周期。Cry2tm1JhjhとWKOで無周期。 | van der Horst1999 |
| Cry1tm1Asn | KO (Reporter) |
A | 短周期。Cry2tm1AsnとWKOで無周期 | Vitaterna1999 | ||
| mouse Cry2 | Cry2tm1Asn | KO | A | Thresher1998 | ||
| Cry2tm1Jhjh | KO | A | 長周期。Cry1とWKOで無周期。 | van der Horst1999 | ||
| fly cry | cryb (crybaby) (D410N) | EMS | A, R | 短い光パルスによるPhase shiftが起きない。 | Stanewsky1998 | |
| crym (truncates the last 19 aa) | EMS | Hypo | Busza2004 | |||
| cry0 | KO | A, R | crybabyと同様 | Dolezelova2007 | ||
| vrille E4BP4 |
fly vrille | vri1 | EMS | Anti | Homo, letahl, hetero, -0.4~0.8 h |
Blau1999 |
| mouse E4BP4 | NA | - | - | - | ||
| Pdp1 Dbp |
fly Pdp1 | Pdp1P205 | Δ2-3 | A, R | Homo, letahl, hetero, +0.5 h |
Cyran2003 |
| mouse Dbp | Dbptm1Schb (Dbpnull) | KO | Dbp, Tef, Hlf 三重変異で Lethal seizures (てんかん) 活動、時計遺伝子発現は正常 |
Lopez-Molina1997 | ||
| mouse Tef | Teftm1Schb | KO | Gachon2004 | |||
| mouse Hlf | Hlftm1Schb | KO | ||||
| cwo | fly cwo | PBac{WH}stich1f05073 | PBac | 活動リズムの減少 | Lim2006, 松本2006, Kadener2006 | |
| PBac{RB}stich1e04207 | PBac | |||||
| Dec | mouse Dec1 (Sharp2) |
Bhlhe40tm1Tan | KO | CCGの一部で発現低下 | Sun2001 Gréchez-Cassiau2003 |
|
| Bhlhe40tm1Rhli | KO | Jiang2008 | ||||
| Bhlhe40tm1.1Rhli | KO | Jiang2008 | ||||
| mouse Dec2 (Sharp1) |
Bhlhe41tm1Mjro | KO | Rossner2008 | |||
| Rev-erb alpha | mouse Rev-erb a | Nr1d1tm1Ven | KO | Chomez2000 | ||
| Nr1d1tm1Schb | KO | 短周期、光による位相前進の促進 | Preitner2002 | |||
| ROR alpha | mouse Ror a | Rorasg | 自然発生 spontaneous |
短周期(Sato2004) | M: Sidman1962 G: Hamilton1996 |
|
| Roratm1Vgi | KO | die between 24 to 28 days after birth | Dussault1998 | |||
| Roratm1Mba | KO | Steinmayr1998 | ||||
| CK1e CK1d |
hamster CK1epsilon (Mesocricetus auratus) ゴールデンハムスター |
tau （R178C) | 自然発生 spontaneous |
+/+, 24h; +/tau, 22 h; tau/tau, 20 h | M: Ralph1988 G: Lowrey2000 |
|
| mouse CKIe | Csnk1etm1Asil | KO | Point mutation (tauアリル) |
tau/+, 21.8 h; tau/tau, 20.0 h |
Meng2008 | |
| Csnk1etm1.1Asil | KO | Deletion | Meng2008 | |||
| mouse CKId |
CK1delta(D2) | KO, conditinal | Liver-specific disruption, +2 h (Per2::luc) | Etchegaray2009 | ||
| fly double-time (dco) | dcoS (dbtS) | EMS | dcoS/+, 21.8 h; dcoS/dcoS, 18h | M, G: Kloss1998 , Price1998) |
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| dcoL (dbtL) | EMS | dcoL/+, 24.9 h; dcoL/dcoL, 26.8 h | ||||
| sgg Gsk3b |
mouse Gsk3b | Gsk3btm1Jrw | KO | A, R | Lethal E13.5 - E14.5 | Hoeflich2000 |
| Gsk3btm1Grc | KO | A, R | Stankunas2003 | |||
| fly sgg | sgg32/sggM11; sgghs.p | 26 h (sggは発生に必須なので、hs-sggでレスキューして成虫を得た) | Martinek2001 | |||
| sggEP1576 | 21 h (tim-Gal4での過剰発現 | |||||
| Fbxl3 | mouse Fbxl3 | Fbxl3Afh | ENU | Hypo? | Homo, +3 h; hetero, +0.5 ~ 1 h | Godinho2007 |
| Fbxl3Ovtm | ENU | Hypo? | Homo, +3 h; hetero, +0.7 h | Siepka2007 | ||
| slmb | fly slmb | slmb8 slmbL.hs | Arrhythmic (無周期)(slmbは発生に必須なので、hs-slmbでレスキューして成虫を得た) | Grima2002 | ||