0024 Decreased circadian period associated with enhanced autophagy in cereblon knockout mice

Abstract Introduction The circadian rhythm plays a critical role in many biological processes. Recently, autophagy was suggested as regulating factor of by reducing protein trafficking. Cereblon (CRBN) is component the E3 ubiquitin ligase complex for ubiquitination and degradation target proteins. Interestingly, cereblon ubiquitinates beclin 1, potent inducer. Accordingly, changes are likely to affect rhythm. However, how can regulate not understood yet. Therefore, we hypothesized that might be an important regulator sought investigate relationship. Methods We obtained 3-month-old CRBN gene knockout (KO) wild-type (WT) mice (n=4 8, respectively). were housed wheel-based activity recording system under 12:12 light-dark (LD) condition 1 week constant darkness (DD) subsequent 2 weeks. Activity data analyzed ClockLab Analysis 6 (Actimetrics, USA). Autophagy-related proteins, including beclin1, microtubule-associated light chain-3 (LC3), p63, measured ELISA western blot. Results found KO showed decreased period during (23.7 vs 23.4 hours, p< 0.05). latency from light-off time initiating activities dark shorter WT mice. Protein analysis assay revealed LC3, p62 increased mice, indicating autophagy. Conclusion Our results demonstrated periods reduced autophagy-related molecules. interpret lack resulted beclin1 triggers As per Beesley et al (2020), autophagy-induced decrease cytoplasmic congestion facilitates trafficking crucial components molecular clock. primarily due enhanced autophagy, although its implication general health unclear. Taken together, suggest associated with via controlling Further investigations understand amplitude shortened needed. Support (if any)