Fig. 1. Ablation of UBR4 in GABAergic neurons impairs activity rhythms under constant light.

a In situ hybridization analysis of Ubr4 (green) mRNA expression in the SCN of control and Ubr4 cKO mice. DAPI, magenta. Scale bar, 100 μm. b Western blots of UBR4 and actin in SCN lysates from control and Ubr4 cKO mice. Full-length UBR4 (~570 kDa), asterisk. c, h Representative actograms displaying wheel-running activities of control and Ubr4 cKO mice under LD and DD conditions (c), or under LL conditions where the light intensity was increased in a stepwise fashion (h). CT 15 light pulse, orange circle (in c). Periods of light are shaded in yellow. d Period length under DD. e, f Daily wheel-running activity (e) and Χ² periodogram amplitude (f) under LD and DD. g Phase shift following a CT15 light pulse. i–l Period length (i), Χ² periodogram amplitude (j), Fast Fourier Transformation (FFT) amplitude (k), and daily wheel-running activity (l) under LL as a function of light intensity. Values represent mean ± SEM. Exact sample size and p-value for all behavioral measures are provided in Supplementary Table 1. *p < 0.05, **p < 0.01, ***p < 0.001 vs. control by two-tailed unpaired t test (d, g) or linear mixed-effects modeling with Bonferroni’s post hoc (e, f, i–l). n.s. not significant.