title: Longitudinal in vivo muscle function analysis of the DMSXL mouse model of myotonic dystrophy type 1.
abstract: Myotonic dystrophy is the most common adult muscle dystrophy. In view of emerging therapies, which use animal models as a proof of principle, the development of reliable outcome measures for in vivo longitudinal study of mouse skeletal muscle function is becoming crucial. To satisfy this need, we have developed a device to measure ankle dorsi- and plantarflexion torque in rodents. We present an in vivo 8-month longitudinal study of the contractile properties of the skeletal muscles of the DMSXL mouse model of myotonic dystrophy type 1. Between 4 and 12 months of age, we observed a reduction in muscle strength in the ankle dorsi- and plantarflexors of DMSXL compared to control mice although the strength per muscle cross-section was normal. Mild steady myotonia but no abnormal muscle fatigue was also observed in the DMSXL mice. Magnetic resonance imaging and histological analysis performed at the end of the study showed respectively reduced muscle cross-section area and smaller muscle fibre diameter in DMSXL mice. In conclusion, our study demonstrates the feasibility of carrying out longitudinal in vivo studies of muscle function over several months in a mouse model of myotonic dystrophy confirming the feasibility of this method to test preclinical therapeutics.
authors.affiliation: Institut de Myologie, UPMC Univ. Paris 6 UM76, Inserm U974, CNRS UMR7215, F-75651 Paris Cedex 13, France. Electronic address: v.decostre@institut-myologie.org.
authors.forename: Valérie
authors.initials: V
authors.lastname: Decostre
authors.forename: Alban
authors.initials: A
authors.lastname: Vignaud
authors.forename: Béatrice
authors.initials: B
authors.lastname: Matot
authors.forename: Aline
authors.initials: A
authors.lastname: Huguet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ledoux
authors.forename: Emilie
authors.initials: E
authors.lastname: Bertil
authors.forename: Bernard
authors.initials: B
authors.lastname: Gjata
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Carlier
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gourdon
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D006614:Hindlimb / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D053581:Muscle Strength Dynamometer; D018482:Muscle, Skeletal / Q000473:pathology*; D009223:Myotonic Dystrophy / Q000235:genetics / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D017346:Protein Serine-Threonine Kinases
keywords: Follow-up; In vivo; Mouse; Myotonic dystrophy type 1; Skeletal muscle