AUTHOR=Rossi Rachele , Falzarano Maria Sofia , Osman Hana , Armaroli Annarita , Scotton Chiara , Mantuano Paola , Boccanegra Brigida , Cappellari Ornella , Schwartz Elena , Yuryev Anton , Mercuri Eugenio , Bertini Enrico , D’Amico Adele , Mora Marina , Johansson Camilla , Al-Khalili Szigyarto Cristina , De Luca Annamaria , Ferlini Alessandra TITLE=Circadian Genes as Exploratory Biomarkers in DMD: Results From Both the mdx Mouse Model and Patients JOURNAL=Frontiers in Physiology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.678974 DOI=10.3389/fphys.2021.678974 ISSN=1664-042X ABSTRACT=

Duchenne muscular dystrophy (DMD) is a rare genetic disease due to dystrophin gene mutations which cause progressive weakness and muscle wasting. Circadian rhythm coordinates biological processes with the 24-h cycle and it plays a key role in maintaining muscle functions, both in animal models and in humans. We explored expression profiles of circadian circuit master genes both in Duchenne muscular dystrophy skeletal muscle and in its animal model, the mdx mouse. We designed a customized, mouse-specific Fluidic-Card-TaqMan-based assay (Fluid-CIRC) containing thirty-two genes related to circadian rhythm and muscle regeneration and analyzed gastrocnemius and tibialis anterior muscles from both unexercised and exercised mdx mice. Based on this first analysis, we prioritized the 7 most deregulated genes in mdx mice and tested their expression in skeletal muscle biopsies from 10 Duchenne patients. We found that CSNK1E, SIRT1, and MYOG are upregulated in DMD patient biopsies, consistent with the mdx data. We also demonstrated that their proteins are detectable and measurable in the DMD patients’ plasma. We suggest that CSNK1E, SIRT1, and MYOG might represent exploratory circadian biomarkers in DMD.