title: Presymptomatic biochemical changes in hindlimb muscle of G93A human Cu/Zn superoxide dismutase 1 transgenic mouse model of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is primarily a motor neuron disorder. Intriguingly, early muscle denervation preceding motor neuron loss is observed in mouse models of ALS. Enhanced muscle vulnerability to denervation process has been suggested by accelerated muscle deterioration following peripheral nerve injury in an ALS mouse model. Here we provide evidence of biochemical changes in the hindlimb muscle of young, presymptomatic G93A hSOD1 transgenic mice. In this report, we demonstrate that cdk5 activity is reduced in hindlimb muscle of 27-day-old G93A hSOD1 transgenic mice. In vitro analysis revealed mutant hSOD1-mediated suppression of cdk5 activity. Furthermore, the decrease in muscle cdk5 activity was accompanied by a significant reduction in MyoD and cyclin D1 levels. These early muscle changes raise the possibility that the progressive deterioration of muscle function is potentiated by altered muscle biochemistry in these mice at a very young, presymptomatic age.
authors.affiliation: Department of Paediatrics and Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4 Canada. kpark@cmmt.ubc.ca <kpark@cmmt.ubc.ca>
authors.forename: Kevin H J
authors.initials: KH
authors.lastname: Park
authors.forename: Inez
authors.initials: I
authors.lastname: Vincent
mesh_terms: D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D056741:Cyclin D; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004195:Disease Models, Animal; D006614:Hindlimb; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism*; D009154:Mutation; D017570:MyoD Protein / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D056741:Cyclin D; D016213:Cyclins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse