PXD005131

PXD005131 is an original dataset announced via ProteomeXchange.

Title	Expression of ALS-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype
Description	Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease characterised by the loss of upper and lower motor neurons. Approximately 10% of ALS cases have a known family history of the disease and mutations in multiple genes have been identified. ALS-linked mutations in CCNF were recently reported, however the pathogenic mechanisms associated with these mutations are yet to be established. To investigate possible mechanisms, an in vitro model of ALS was developed that expressed mutant CCNF in a neuronal cell line (Neuro-2a). Proteomic analysis of this in vitro model identified the disruption of several cellular pathways, including those associated with caspase-3 mediated cell death and axonal outgrowth. To establish whether these findings were replicated in vivo, a zebrafish model was developed. Transient overexpression of human mutant CCNF in zebrafish led to increased caspase-3 activity, increased cell death and a motor neuron axonopathy consisting of shortened primary motor axons and increased frequency of aberrant axonal branching. A significant correlation between the severity of this mutant CCNF-induced axonopathy and reduced motor function was also demonstrated in this model, with zebrafish expressing the mutant protein demonstrating an impaired motor response to a light stimulus. This is the first report of an ALS-linked CCNF mutation in vivo and indicates that zebrafish will be a useful tool to model the pathogenesis of CCNF-linked motor neuron degeneration.
HostingRepository	PRIDE
AnnounceDate	2017-05-22
AnnouncementXML	Submission_2017-05-22_00:09:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-11 03:41:50	ID requested
⏵ 1	2017-05-22 00:09:42	announced

Hogan AL, Don EK, Rayner SL, Lee A, Laird AS, Watchon M, Winnick C, Tarr IS, Morsch M, Fifita JA, Gwee SSL, Formella I, Hortle E, Yuan KC, Molloy MP, Williams KL, Nicholson GA, Chung RS, Blair IP, Cole NJ, Expression of ALS/FTD-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype. Hum Mol Genet, 26(14):2616-2626(2017) [pubmed]

curator keyword: Biological

submitter keyword: motor neurone disease, amyotrophic lateral sclerosis, zebrafish

Dr. Albert Lee
contact affiliation	Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, North Ryde, NSW, 2109, Australia
contact email	albert.lee@mq.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005131
     1. Label: PRIDE project
     2. Name: Expression of ALS-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype