title: Comparison of skeletal muscle pathology and motor function of dystrophin and utrophin deficient mouse strains.
abstract: The genetic defect of mdx mice resembles that of Duchenne muscular dystrophy, although their functional performance and life expectancy is nearly normal. By contrast, mice lacking utrophin and dystrophin (mdx/utrn -/-) are severely affected and die prematurely. Mice with one utrophin allele (mdx/utrn +/-) are more severely affected than mdx mice, but outlive mdx/utrn -/- mice. We subjected mdx/utrn +/+, +/-, -/- and wild type males to a 12week functional test regime of four different functional tests. Mdx/utrn +/+ and +/- mice completed the regime, while mdx/utrn -/- mice died prematurely. Mdx/utrn +/- mice performed significantly worse compared to mdx/utrn +/+ mice in functional tests. Creatine kinase levels, percentage of fibrotic/necrotic tissue, morphology of neuromuscular synapses and expression of biomarker genes were comparable, whereas mdx/utrn +/- and -/- mice had increased levels of regenerating fibers. This makes mdx/utrn +/- mice valuable for testing the benefit of potential therapies on muscle function parameters.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: van Putten
authors.forename: Darshan
authors.initials: D
authors.lastname: Kumar
authors.forename: Margriet
authors.initials: M
authors.lastname: Hulsker
authors.forename: Willem M H
authors.initials: WM
authors.lastname: Hoogaars
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: Annemarieke
authors.initials: A
authors.lastname: van Opstal
authors.forename: Maarten
authors.initials: M
authors.lastname: van Iterson
authors.forename: Peter
authors.initials: P
authors.lastname: Admiraal
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.forename: Annemieke
authors.initials: A
authors.lastname: Aartsma-Rus
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis; D049411:Utrophin / Q000172:deficiency / Q000378:metabolism*
chemical_list: D016189:Dystrophin; D049411:Utrophin