| First Author | Okano S | Year | 2009 |
| Journal | Neurosci Lett | Volume | 451 |
| Issue | 3 | Pages | 246-51 |
| PubMed ID | 19159659 | Mgi Jnum | J:146522 |
| Mgi Id | MGI:3837872 | Doi | 10.1016/j.neulet.2009.01.014 |
| Citation | Okano S, et al. (2009) Unusual circadian locomotor activity and pathophysiology in mutant CRY1 transgenic mice. Neurosci Lett 451(3):246-51 |
| abstractText | In the widely accepted molecular model underlying mammalian circadian rhythm, cryptochrome proteins (CRYs) play indispensable roles as inhibitive components of the CLOCK-BMAL1-mediated transcriptional-translational negative feedback loop. In order to clarify yet uncovered aspects of mammalian CRYs in vivo, we generated transgenic (Tg) mice ubiquitously overexpressing CRY1 as well as CRY1 having a mutation in the dipeptide motif of cysteine and proline that is conserved beyond evolutional divergence among animal CRYs: cysteine414 of the motif was replaced with alanine (CRY1-AP). The mice overexpressing CRY1 (CRY1 Tg) exhibited robust circadian rhythms of locomotor activity. In sharp contrast, the mice overexpressing CRY1-AP (CRY1-AP Tg) displayed a unique circadian phenotype. Their locomotor free-running periods were very long (around 28h) with rhythm splitting: the bout of activity of CRY1-AP Tg mice was split into two equal components in constant darkness. Moreover, CRY1-AP Tg mice displayed abnormal entrainment behavior: their bout of activity shifted immediately in response to a shift of the light-dark cycles. In addition, we found that CRY1-AP Tg mice showed symptoms characteristic of diabetes mellitus. The results indicate that the motif of CRY1 is crucial to the mammalian clock system and physiology. |
