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Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

Wager, K; Zdebik, AA; Fu, S; Cooper, JD; Harvey, RJ; Russell, C; (2016) Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease). PLoS One , 11 (6) , Article e0157365. 10.1371/journal.pone.0157365. Green open access

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Abstract

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80-85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery.

Type: Article
Title: Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0157365
Publisher version: http://dx.doi.org/10.1371/journal.pone.0157365
Language: English
Additional information: Copyright © 2016 Wager et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: http://discovery.ucl.ac.uk/id/eprint/1501138
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