title: Neuronal over-expression of chromogranin A accelerates disease onset in a mouse model of ALS.
abstract: Recent studies provided evidence that chromogranins can interact with mutant superoxide dismutase 1 (SOD1) and that chromogranin B (CgB) may act as a susceptibility gene and modifier of onset in amyotrophic lateral sclerosis (ALS). To further investigate the role of chromogranins in ALS pathogenesis, we generated SOD1(G37R) mice that over-express CgA under the control of Thy1 promoter. Here, we report that neuronal over-expression of CgA in SOD1(G37R) mice caused acceleration of onset of motor impairment and exacerbation of motor neuron degeneration. The use of monoclonal antibody specific to misfolded mutant SOD1 demonstrated a higher level of misfolded SOD1 species in double transgenic mice compared to SOD1(G37R) mice, suggesting a stabilization of pathogenic SOD1 species by excess CgA. These results suggest a role of chromogranins as modulators of disease onset in ALS pathogenesis.
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec, Laval University, Quebec, Quebec, Canada.
authors.forename: Samer Abou
authors.initials: SA
authors.lastname: Ezzi
authors.forename: Roxanne
authors.initials: R
authors.lastname: Larivière
authors.forename: Makoto
authors.initials: M
authors.lastname: Urushitani
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002470:Cell Survival; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009469:Neuromuscular Junction / Q000473:pathology; D017510:Protein Folding; D013116:Spinal Cord / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics; D018800:Thy-1 Antigens / Q000235:genetics
chemical_list: D053379:Chromogranin A; D005904:Glial Fibrillary Acidic Protein; D018800:Thy-1 Antigens; C470429:SOD1 G37R protein, mouse; D013482:Superoxide Dismutase