Usp2 knockout (KO) mice exhibit disrupted entrainment of to light cues at dusk.
USP2 is involved in regulating circadian rhythms, which follow a ~24-hour cycle.
The expression of Usp2 is found throughout the suprachiasmatic nucleus (SCN) and in the retina.
Usp2 KO mice have intact retinal structure and normal photoreception, indicating USP2's action is not in the retina.
Knocking out Usp2 in the SCN leads to a light entrainment phenotype similar to that of full-body KO mice.
In the SCN, Usp2 KO mice show reduced induction of the clock gene Per1 and decreased activation of the MAPK/ERK pathway in response to light.
Simplified
Ubiquitin-specific peptidase 2 (USP2) is a (DUB) with a diversity of functions in physiology. One of these functions is the regulation of , which are physiological rhythms with a period of ~24 h. Previous studies have indicated a role for USP2 in , the process by which circadian clocks synchronize to environmental light cues. Here, we investigated the implication of USP2 in this process, using Usp2 knockout (KO) mice. Using different light treatments and running wheel recordings, we established that USP2 controls entrainment of the clock to light cues at dusk. Further, we showed that Usp2 is expressed throughout the suprachiasmatic nucleus (SCN), the site of the central clock, and in the retina. This raised the question of where USP2 acts on circadian photoreception. We found that it is not within the retina, as retinas of Usp2 KO mice have an intact structure and unaltered photoreception through intrinsically photosensitive retinal ganglion cells. Moreover, KO of Usp2 within the retina does not alter clock entrainment to light. In contract, KO of Usp2 in the SCN causes a light entrainment phenotype similar to full-body KO mice, showing that the action of USP2 in modulating photic entrainment predominantly takes place in the SCN. Finally, within the SCN, we found that induction of clock gene Per1 and activation of MAPK/ERK pathway in response to light were blunted in Usp2 KO mice. Altogether, we established a key role for USP2 in regulating photic entrainment by modulating light-responsive pathways within the SCN.
Key numbers
0.0302
Phase Shift Difference
Statistical significance of phase shift differences in response to light pulses.
0.0022
Light-Induced Per1 Induction
Statistical significance of Per1 induction levels post-light pulse.
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