RT Journal Article
SR Electronic
T1 Desmin is a modifier of dystrophic muscle features in Mdx mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 742858
DO 10.1101/742858
A1 Ferry, Arnaud
A1 Messéant, Julien
A1 Parlakian, Ara
A1 Lemaitre, Mégane
A1 Roy, Pauline
A1 Delacroix, Clément
A1 Lilienbaum, Alain
A1 Hovhannisyan, Yeranuhi
A1 Furling, Denis
A1 Klein, Arnaud
A1 Li, Zhenlin
A1 Agbulut, Onnik
YR 2019
UL http://biorxiv.org/content/early/2019/08/23/742858.abstract
AB Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease, caused by dystrophin deficiency. Desmin is like dystrophin associated to costameric structures bridging sarcomeres to extracellular matrix that are involved in force transmission and skeletal muscle integrity. In the present study, we wanted to gain further insight into the roles of desmin which expression is increased in the muscle from the mouse Mdx DMD model. We show that a deletion of the desmin gene (Des) in Mdx mice (DKO, Mdx:desmin-/-) induces a marked worsening of the weakness (reduced maximal force production) as compared to Mdx mice. Fragility (higher susceptibility to contraction-induced injury) was also aggravated and fatigue resistance was reduced in DKO mice. Moreover, in contrast to Mdx mice, the DKO mice did not undergo a muscle hypertrophy because of smaller and less numerous fibers, with reduced percentage of centronucleated fibres. Interestingly, Desmin cDNA transfer with adeno-associated virus in 1-month-old DKO mice and newborn Mdx mice improved muscle weakness. Overall, desmin plays important and beneficial roles on muscle performance, fragility and remodelling in dystrophic Mdx mice.