title: Genetic models of C9orf72: what is toxic?
abstract: A hexanucleotide repeat expansion in the gene C9orf72 is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Pathogenesis may occur either due to loss of function of the C9orf72 gene, or a toxic gain of function, via the production of repetitive sense and antisense RNA and/or repetitive dipeptide repeat proteins. Recently, mouse knockouts have suggested that a loss of function of C9orf72 alone is insufficient to lead to neurodegeneration, whilst overexpression of hexanucleotide DNA is sufficient in a wide range of model systems. Additionally, models have now been created to attempt to study the effects of repetitive RNA and dipeptide proteins in isolation and thus determine their relevance to disease.
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK; Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Moens
authors.affiliation: Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Robert-Koch-Str. 21, 50931 Cologne, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK. Electronic address: a.isaacs@ucl.ac.uk.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Isaacs
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000073885:C9orf72 Protein / Q000235:genetics*; D004151:Dipeptides / Q000235:genetics; D004195:Disease Models, Animal; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004151:Dipeptides