Toggle Main Menu Toggle Search

Open Access padlockePrints

Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy

Lookup NU author(s): Elena Martoni, Professor Hanns Lochmuller, Professor Volker Straub, Emerita Professor Katherine Bushby

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1(-/-) mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1(-/-) (also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.


Publication metadata

Author(s): Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmuller H, Straub V, Bushby K, Castrignano T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang XP, Hodge BA, Esser KA, Ferlini A

Publication type: Article

Publication status: Published

Journal: Journal of Cell Science

Year: 2016

Volume: 129

Issue: 8

Pages: 1671-1684

Print publication date: 15/04/2016

Online publication date: 04/03/2016

Acceptance date: 16/02/2016

ISSN (print): 0021-9533

ISSN (electronic): 1477-9137

Publisher: The Company of Biologists Ltd

URL: http://dx.doi.org/10.1242/jcs.175927

DOI: 10.1242/jcs.175927


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share