Role of Mouse Cryptochrome Blue-Light Photoreceptor in Circadian Photoresponses

Abstract

Cryptochromes are photoactive pigments in the eye that have been proposed to function as circadian photopigments. Mice lacking the cryptochrome 2 blue-light photoreceptor gene (mCry2) were tested for circadian clock-related functions. The mutant mice had a lower sensitivity to acute light induction of mPer1 in the suprachiasmatic nucleus (SCN) but exhibited normal circadian oscillations of mPer1 and mCry1 messenger RNA in the SCN. Behaviorally, the mutants had an intrinsic circadian period about 1 hour longer than normal and exhibited high-amplitude phase shifts in response to light pulses administered at circadian time 17. These data are consistent with the hypothesis that CRY2 protein modulates circadian responses in mice and suggest that cryptochromes have a role in circadian photoreception in mammals.

Nuclear localization of the Arabidopsis blue light receptor cryptochrome 2

“…The fact that related proteins, which have blue light photoreceptor function, synchronize circadian rhythms in organisms as distantly related as plants and mammals is very interesting from an evolutionary point of view. Furthermore, results presented here which demonstrate that Arabidopsis CRY2 is localized within the nucleus as is Cry2 in mice and humans (Kobayashi et al, 1998;Thresher et al, 1998) may well be very important for the further understanding of the molecular mechanism by which the light signal is transduced to the clock. Studies on the circadian rhythm of cab gene transcription in photoreceptor mutants demonstrate that besides cryptochromes, phytochromes also entrain the circadian clock (Somers et al, 1998).…”

“…By database searching we identi®ed in the C-terminal region of CRY2 a nuclear localization sequence (NLS; amino acid positions 541±558), which belongs to the group of bipartite NLS ( Figure 2). The CRY2 NLS is very similar to NLS of proteins, for which nuclear localization has already been demonstrated (Go È rlich and Mattaj, 1996;Kobayashi et al, 1998;Thresher et al, 1998).…”

“…Mice mutated in Cry2 showed an increased phase shift in circadian rhythm in response to light pulses. In addition, the freerunning period was extended, indicating that mCry2 is a photoreceptor which entrains the endogenous oscillator and interacts with components of the circadian clock (Thresher et al, 1998). The Arabidopsis cry2 mutant is delayed in¯owering under long-day conditions compared to the wild type .…”

“…The genes were named hCry1, hCry2 (human) and mCry1, mCry2 (mouse), respectively (Hsu et al, 1996;Kobayashi et al, 1998). Mice strains lacking the Cry2 gene had a reduced photic sensitivity and increased phase shifts in response to light, indicating that mCry2 has a role in circadian photoreception (Thresher et al, 1998). In addition, mCry2 deletion led to a lengthening of the freerunning period in constant darkness, whereas mice Cry1 mutants had an accelerated free-running periodicity of locomoter activity.…”

A Novel Human Opsin in the Inner Retina

“…Two cryptochromes (mCRY1 and mCRY2) have been localized to ganglion and inner nuclear cells and have been proposed as candidate circadian photopigments. Knock-out mice missing one or both cryptochromes have been constructed to assess their role in circadian rhythm regulation (Thresher et al, 1998;van der Horst et al, 1999). One would expect the phenotype of a circadian photopigment-deficient mouse to be like that of a bilaterally enucleated mouse (Nelson and Zucker, 1981).…”