title: Altered expression of myogenic regulatory factors in the mouse model of amyotrophic lateral sclerosis.
abstract: BACKGROUND
  In the superoxide dismutase 1 (SOD1)-G93A mouse model of amyotrophic lateral sclerosis (ALS), skeletal muscle is a key target of mutant SOD1 toxicity. However, the expression of factors that control the regenerative potential of the muscle is unknown in this model.
  
  
  OBJECTIVE
  To characterize the expression of satellite cell marker Pax7 and myogenic regulatory factors (MRF) in skeletal muscle of SOD1-G93A mice at different stages of the disease.
  
  
  METHODS
  The expressions of Pax7, Myod1, Myf5 and myogenin (Myog) were determined by quantitative real-time PCR and by Western blotting from the grouped gastrocnemius, quadriceps and soleus muscles of SOD1-G93A mice at presymptomatic, symptomatic and terminal stages of the disease, and from surgically denervated wild-type gastrocnemius muscles.
  
  
  RESULTS
  Pax7 mRNA and MYF5 protein were upregulated in presymptomatic mice, coinciding with increased muscle damage marker Rrad and chemokine Ccl5. All MRF transcripts and most proteins (excluding MYOG) were increased, starting from 3 months of age, simultaneously with increased expression of denervation marker Chrna1. However, in the terminal stage, no protein increase was evident for Pax7 or any of the MRF despite the increased mRNA levels. The transcripts for chemokine Ccl2 and chemokine receptor Cxcr4 were increased starting from the onset of symptoms.
  
  
  CONCLUSIONS
  The characterization of Pax7 and MRF in SOD1-G93A mice reveals a progressive induction of the myogenic program at the RNA level, but a blunted protein level response at late stages of the disease. Altered posttranscriptional and posttranslational mechanisms likely to operate, as well as the potential role of chemokine signaling in mutant SOD1 muscle, are discussed.
authors.affiliation: LAGENBIO-I3A, Aragón Institute of Health Sciences (IACS), Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Manzano
authors.forename: Janne M
authors.initials: JM
authors.lastname: Toivonen
authors.forename: Sara
authors.initials: S
authors.lastname: Oliván
authors.forename: Ana C
authors.initials: AC
authors.lastname: Calvo
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno-Igoa
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Muñoz
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.forename: Alberto
authors.initials: A
authors.lastname: García-Redondo
authors.forename: Rosario
authors.initials: R
authors.lastname: Osta
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis* / Q000235:genetics; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018006:Myogenic Regulatory Factors; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase