Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)
| Autor: | Kim, Wager, Anselm A, Zdebik, Sonia, Fu, Jonathan D, Cooper, Robert J, Harvey, Claire, Russell |
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| Rok vydání: | 2015 |
| Předmět: |
Physiology
Apoptosis Biochemistry Morpholinos Larvae Medicine and Health Sciences Gliosis Zebrafish Clinical Neurophysiology Brain Mapping Behavior Animal Cell Death Neuronal Morphology Fishes Brain Electroencephalography Animal Models Mitochondrial Proton-Translocating ATPases Electrophysiology Bioassays and Physiological Analysis Brain Electrophysiology Osteichthyes Cell Processes Gene Knockdown Techniques Vertebrates Cellular Structures and Organelles Anatomy Research Article Imaging Techniques Ocular Anatomy Neurophysiology Neuroimaging Motor Activity Research and Analysis Methods Retina Model Organisms Neuronal Ceroid-Lipofuscinoses Ocular System Diagnostic Medicine Animals RNA Antisense Cell Proliferation Epilepsy Metamorphosis Myocardium Electrophysiological Techniques Organisms Biology and Life Sciences Proteins Cell Biology Zebrafish Proteins Survival Analysis Axons Chaperone Proteins Disease Models Animal Protein Subunits Cellular Neuroscience Nerve Degeneration Lysosomes Developmental Biology Neuroscience |
| Zdroj: | PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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