title: Human embryonic stem cell-derived motor neurons expressing SOD1 mutants exhibit typical signs of motor neuron degeneration linked to ALS.
abstract: Human embryonic stem cell (hESC)-derived neurons have the potential to model neurodegenerative disorders. Here, we demonstrate the expression of a mutant gene, superoxide dismutase 1(SOD1), linked to familial amyotrophic lateral sclerosis (ALS) in hESC-derived motor neurons. Green fluorescent protein (GFP) expression under the control of the HB9 enhancer was used to identify SOD1-transfected motor neurons that express human wild-type SOD1 or one of three different mutants (G93A, A4V and I113T) of SOD1. Neurons transfected with mutant SOD1 exhibited reduced cell survival and shortened axonal processes as compared with control-transfected cells, which could survive for 3 weeks or more. The results indicate that hESC-derived cell populations can be directed to express disease-relevant genes and to display characteristics of the disease-specific cell type. These genetically manipulated hESC-derived motor neurons can facilitate and advance the study of disease-specific cellular pathways, and serve as a model system to test new therapeutic approaches.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Karumbayaram
authors.forename: Theresa K
authors.initials: TK
authors.lastname: Kelly
authors.forename: Andres A
authors.initials: AA
authors.lastname: Paucar
authors.forename: Anne J T
authors.initials: AJ
authors.lastname: Roe
authors.forename: Joy A
authors.initials: JA
authors.lastname: Umbach
authors.forename: Andrew
authors.initials: A
authors.lastname: Charles
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
authors.forename: Harley I
authors.initials: HI
authors.lastname: Kornblum
authors.forename: Martina
authors.initials: M
authors.lastname: Wiedau-Pazos
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D004594:Electrophysiology / Q000379:methods; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013997:Time Factors
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002118:Calcium