title: Proteomic analysis of the Rett syndrome experimental model mecp2Q63Xmutant zebrafish.
abstract: Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Recently, a zebrafish carrying a mecp2-null mutation has been developed with the resulting phenotypes exhibiting defective sensory and thigmotactic responses, and abnormal motor behavior reminiscent of the human disease. Here, we performed a proteomic analysis to examine protein expression changes in mecp2-null vs. wild-type larvae and adult zebrafish. We found a total of 20 proteins differentially expressed between wild-type and mutant zebrafish, suggesting skeletal and cardiac muscle functional defects, a stunted glycolysis and depleted energy availability. This molecular evidence is directly linked to the mecp2-null zebrafish observed phenotype. In addition, we identified changes in expression of proteins critical for a proper redox balance, suggesting an enhanced oxidative stress, a phenomenon also documented in human patients and RTT murine models. The molecular alterations observed in the mecp2-null zebrafish expand our knowledge on the molecular cascade of events that lead to the RTT phenotype.
  
  
  
  We performed a proteomic study of a non-mammalian vertebrate model (zebrafish, Danio rerio) for Rett syndrome (RTT) at larval and adult stages of development. Our results reveal major protein expression changes pointing out to defects in energy metabolism, redox status imbalance, and muscle function, both skeletal and cardiac. Our molecular analysis grants the mecp2-null zebrafish as a valuable RTT model, triggering new research approaches for a better understanding of the RTT pathogenesis and phenotype expression. This non-mammalian vertebrate model of RTT strongly suggests a broad impact of Mecp2 dysfunction.
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy; Clinical Pathology Laboratory Unit, University Hospital, AOUS, Siena, Italy. Electronic address: alessio.cortelazzo@biologo.onb.it.
authors.forename: Alessio
authors.initials: A
authors.lastname: Cortelazzo
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietri
authors.affiliation: Neonatal Intensive Care Unit, University Hospital, AOUS, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy; Clinical Pathology Laboratory Unit, University Hospital, AOUS, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Guerranti
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.affiliation: Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Timperio
authors.affiliation: Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy.
authors.forename: Lello
authors.initials: L
authors.lastname: Zolla
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D007814:Larva / Q000737:chemistry; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009132:Muscles / Q000502:physiology; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000032:analysis / Q000502:physiology; D040901:Proteomics / Q000379:methods; D015518:Rett Syndrome / Q000235:genetics*; D015027:Zebrafish
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D011506:Proteins
keywords: Energy metabolism; Muscle; Oxidative stress; Rett syndrome; Zebrafish