Table 1.
Behavioral phenotypes of mutations in mouse clock and clock-related genes
| Gene(s) | Protein product(s) | Mutant allele(s) | Mutant phenotype(s) | References |
|---|---|---|---|---|
| Clock | bHLH-PAS transcription factor |
ClockΔ19/Δ19 Clock−/− |
4 hr longer pd/arrhythmic 0.4 hr shorter pd |
(Vitaterna et al., 1994) (Debruyne et al., 2006) |
| Npas2 (Mop4) | bHLH-PAS transcription factor | Npas2−/− | 0.2 hr shorter pd | (Dudley et al., 2003) |
| Clock/Npas2 | bHLH-PAS transcription factors | Clock−/−/Npas2−/− | Arrhythmic | (DeBruyne et al., 2007a) |
| Bmal1 (Arntl, Mop3) | bHLH-PAS transcription factor | Bmal1−/− | Arrhythmic | (Bunger et al., 2000) |
| Cry1 | flavoprotein | Cry1−/− | 1 hr shorter pd | (van der Horst et al., 1999; Vitaterna et al., 1999) |
| Cry2 | flavoprotein | Cry2−/− | 1 hr longer pd | (Thresher et al., 1998; van der Horst et al., 1999) |
| Cry1/Cry2 | flavoproteins | Cry1−/−/Cry2−/− | Arrhythmic | (van der Horst et al., 1999; Vitaterna et al., 1999) |
| Per1 | PAS protein | Per1−/− | 0.7 hr shorter pd | (Cermakian et al., 2001) |
| Per1brdml | 1 hr shorter pd | (Zheng et al., 2001) | ||
| Per1ldc | 0.5 hr shorter pd/arrhythmic | (Bae et al., 2001) | ||
| Per2 | PAS protein | Per2brdml | 1.5 hr shorter pd/arrhythmic | (Zheng et al., 1999) |
| Per2ldc | Arrhythmic | (Bae et al., 2001) | ||
| Per3 | PAS protein | Per3−/− | 0–0.5 hr shorter pd | (Shearman et al., 2000a) |
| Per1/Per2 | PAS proteins | Per1brdml/Per2brdml | Arrhythmic | (Zheng et al., 2001) |
| Per1brdml/Per2brdml | Arrhythmic | (Bae et al., 2001) | ||
| Per1/Cry1 | PAS protein/flavoprotein | Per1brdml/Cry1−/− | Normal behavior | (Oster et al., 2003) |
| Per1/Cry2 | PAS protein/flavoprotein | Per1brdm1/Cry2−/− | <6 months, 1.5 hr longer pd; >6 months, arrhythmic |
(Oster et al., 2003) |
| Per2/Cry1 | PAS protein/flavoprotein | Per2brdm1/Cry1−/− | Arrhythmic | (Oster et al., 2002) |
| Per2/Cry2 | PAS protein/flavoprotein | Per2brdm1/Cry2−/− | 0–0.4 hr shorter pd | (Oster et al., 2002) |
| Rev-erbα (Nr1d1) | nuclear receptor | Rev-erbα−/− | 0.5 hr shorter pd; disrupted entrainment |
(Preitner et al., 2002) |
| Rev-erbβ (Nr1d2) | nuclear receptor | — | — | — |
| Rorα (Rora) | nuclear receptor | Rorα−/− (staggerer) | 0.5 hr shorter pd; disrupted entrainment |
(Sato et al., 2004) |
| Rorβ (Rorb) | nuclear receptor | Rorβ−/− | 0.5 hr longer pd | (Masana et al., 2007) |
| Rorγ (Rorc) | nuclear receptor | Rorγ−/− | Normal behavior | (Liu et al., 2008) |
| Dec1 (Bhlhe40, Stra13, Sharp-2) | bHLH transcription factor | Stra13−/− | 0.15 hr longer pd | (Nakashima et al., 2008) |
| Dec2 (Bhlhe41, Sharp-1) | bHLH transcription factor | Sharp-1−/− | Delayed resetting | (Rossner et al., 2008) |
| CK1δ (Csnk1d) | casein kinase 1 | CK1δ+/− | 0–0.5 hr longer pd | (Xu et al., 2005; Etchegaray et al., 2009) |
| CK1ε (Csnk1e) | casein kinase 1 | CK1ε−/− | 0.2–0.4 hr longer pd | (Meng et al., 2008; Etchegaray et al., 2009) |
| *CK1εtau | 4 hr shorter pd | (Lowrey et al., 2000; Meng et al., 2008) |
||
| CK1α (Csnk1a1) | casein kinase 1 | — | — | — |
| Fbxl3 | F-box protein | Fbxl3Ovtm | 2 hr longer pd | (Siepka et al., 2007) |
| Fbxl3Afh | 3 hr longer pd | (Godinho et al., 2007) | ||
| Bmal2 (Arntl2, Mop9, Clif) | bHLH-PAS transcription factor | — | — | — |
| Pgc1a (Ppargc1a) | transcriptional coactivator | Pgc1a−/− | 0.3 hr longer pd | (Liu et al., 2007c) |
| Mtnr1a (Mel1a) | G protein-coupled receptor | Mtnr1a−/− | Normal behavior | (Liu et al., 1997a) |
| Mtnr1b (Mel1b) | G protein-coupled receptor | Mtnr1b−/− | Normal behavior | (Jin et al., 2003) |
| Opn4 | melanopsin; opsin 4 | Opn4−/− | Attenuated photic responses | (Panda et al., 2002b; Ruby et al., 2002) |
| Dbp | PAR bZIP transcription factor | Dbp−/− | 0.5 hr shorter pd | (Lopez-Molina et al., 1997) |
| Vipr2 | G protein-coupled receptor | Vipr2−/− | Disrupted locomotor rhythm | (Harmar et al., 2002; Cutler et al., 2003) |
| Vip | peptide hormone | Vip−/− | 1 hr shorter pd/arrhythmic | (Colwell et al., 2003) |
| Prok2 (PK2) | secreted protein | Prok2−/− | Reduced locomotor activity | (Li et al., 2006) |
| Nocturnin (Ccrn4l) | deadenylase | Noc−/− | Normal behavior | (Green et al., 2007) |
Gene symbols listed here are the predominate forms used in the scientific literature; alternate forms are given in parentheses. When the predominant symbol differs from standard mouse gene nomenclature, the standard form is given in parentheses. For genes with more than two symbols in parentheses, the form adhering to standard mouse gene nomenclature is underlined.
*
First identified as a mutation in Syrian hamster (Mesocricetus auratus).