TY - JOUR
T1 - Circadian Genes as Exploratory Biomarkers in DMD
T2 - Results From Both the mdx Mouse Model and Patients
AU - Rossi, Rachele
AU - Falzarano, Maria Sofia
AU - Osman, Hana
AU - Armaroli, Annarita
AU - Scotton, Chiara
AU - Mantuano, Paola
AU - Boccanegra, Brigida
AU - Cappellari, Ornella
AU - Schwartz, Elena
AU - Yuryev, Anton
AU - Mercuri, Eugenio
AU - Bertini, Enrico
AU - D’Amico, Adele
AU - Mora, Marina
AU - Johansson, Camilla
AU - Al-Khalili Szigyarto, Cristina
AU - De Luca, Annamaria
AU - Ferlini, Alessandra
N1 - Publisher Copyright:
© Copyright © 2021 Rossi, Falzarano, Osman, Armaroli, Scotton, Mantuano, Boccanegra, Cappellari, Schwartz, Yuryev, Mercuri, Bertini, D’Amico, Mora, Johansson, Al-Khalili Szigyarto, De Luca and Ferlini.
PY - 2021/7/8
Y1 - 2021/7/8
N2 - 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.
AB - 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.
KW - biomarker
KW - circadian rhythm
KW - Duchenne muscular dystrophy (DMD)
KW - mdx mice
KW - RNA analysis
KW - skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=85111133996&partnerID=8YFLogxK
U2 - 10.3389/fphys.2021.678974
DO - 10.3389/fphys.2021.678974
M3 - Artículo
AN - SCOPUS:85111133996
SN - 1664-042X
VL - 12
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 678974
ER -