title: Muscle-derived extracellular signal-regulated kinases 1 and 2 are required for the maintenance of adult myofibers and their neuromuscular junctions.
abstract: The Ras-extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway appears to be important for the development, maintenance, aging, and pathology of mammalian skeletal muscle. Yet no gene targeting of Erk1/2 in muscle fibers in vivo has been reported to date. We combined a germ line Erk1 mutation with Cre-loxP Erk2 inactivation in skeletal muscle to produce, for the first time, mice lacking ERK1/2 selectively in skeletal myofibers. Animals lacking muscle ERK1/2 displayed stunted postnatal growth, muscle weakness, and a shorter life span. Their muscles examined in this study, sternomastoid and tibialis anterior, displayed fragmented neuromuscular synapses and a mixture of modest fiber atrophy and loss but failed to show major changes in fiber type composition or absence of cell surface dystrophin. Whereas the lack of only ERK1 had no effects on the phenotypes studied, the lack of myofiber ERK2 explained synaptic fragmentation in the sternomastoid but not the tibialis anterior and a decrease in the expression of the acetylcholine receptor (AChR) epsilon subunit gene mRNA in both muscles. A reduction in AChR protein was documented in line with the above mRNA results. Evidence of partial denervation was found in the sternomastoid but not the tibialis anterior. Thus, myofiber ERK1/2 are differentially required for the maintenance of myofibers and neuromuscular synapses in adult mice.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Seaberg
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Henslee
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA Texas A&M University Institute for Neuroscience, College Station, Texas, USA.
authors.forename: Ximena
authors.initials: X
authors.lastname: Paez-Colasante
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Landreth
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA Texas A&M University Institute for Neuroscience, College Station, Texas, USA mjrimer@medicine.tamhsc.edu.
authors.forename: Mendell
authors.initials: M
authors.lastname: Rimer
mesh_terms: D000818:Animals; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D011950:Receptors, Cholinergic / Q000378:metabolism
chemical_list: D011950:Receptors, Cholinergic; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3