eprintid: 1501138
rev_number: 38
eprint_status: archive
userid: 608
dir: disk0/01/50/11/38
datestamp: 2016-07-01 16:01:06
lastmod: 2021-09-19 22:27:58
status_changed: 2016-07-01 16:01:06
type: article
metadata_visibility: show
creators_name: Wager, K
creators_name: Zdebik, AA
creators_name: Fu, S
creators_name: Cooper, JD
creators_name: Harvey, RJ
creators_name: Russell, C
title: Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G02
divisions: D10
note: 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.
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.
date: 2016-06-21
date_type: published
official_url: http://dx.doi.org/10.1371/journal.pone.0157365
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1137878
doi: 10.1371/journal.pone.0157365
pii: PONE-D-15-54363
lyricists_name: Harvey, Robert
lyricists_name: Zdebik, Anselm
lyricists_id: RHARV50
lyricists_id: AAZDE01
actors_name: Zdebik, Anselm
actors_id: AAZDE01
actors_role: owner
full_text_status: public
publication: PLoS One
volume: 11
number: 6
article_number: e0157365
event_location: United States
issn: 1932-6203
citation:        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 <https://doi.org/10.1371/journal.pone.0157365>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1501138/1/journal.pone.0157365.PDF