PUBLICATION
Functional characterization of a FUS mutant zebrafish line as a novel genetic model for ALS
- Authors
- Bourefis, A.R., Campanari, M.L., Buee-Scherrer, V., Kabashi, E.
- ID
- ZDB-PUB-200508-10
- Date
- 2020
- Source
- Neurobiology of disease 142: 104935 (Journal)
- Registered Authors
- Keywords
- Amyotrophic lateral sclerosis (ALS), FUS, Frontotemporal dementia, Genetics, Motor neuron, Neurodegeneration, Neuromuscular junction, Tau, Zebrafish
- MeSH Terms
-
- Amyotrophic Lateral Sclerosis/genetics*
- Amyotrophic Lateral Sclerosis/pathology
- Animals
- Behavior, Animal/physiology
- Disease Models, Animal*
- Models, Genetic*
- Motor Neurons/pathology
- Mutation
- Neuromuscular Junction/pathology
- RNA-Binding Protein FUS/genetics*
- Zebrafish/genetics*
- PubMed
- 32380281 Full text @ Neurobiol. Dis.
Citation
Bourefis, A.R., Campanari, M.L., Buee-Scherrer, V., Kabashi, E. (2020) Functional characterization of a FUS mutant zebrafish line as a novel genetic model for ALS. Neurobiology of disease. 142:104935.
Abstract
Mutations in Fused in sarcoma (FUS), an RNA-binding protein, are known to cause Amyotrophic Lateral Sclerosis (ALS). However, molecular mechanisms due to loss of FUS function remain unclear and controversial. Here, we report the characterization and phenotypic analysis of a deletion mutant of the unique FUS orthologue in zebrafish where Fus protein levels are depleted. The homozygous mutants displayed a reduced lifespan as well as impaired motor abilities associated with specific cellular deficits, including decreased motor neurons length and neuromuscular junctions (NMJ) fragmentation. Furthermore, we demonstrate that these cellular impairments are linked to the misregulation of mRNA expression of acetylcholine receptor (AChR) subunits and histone deacetylase 4, markers of denervation and reinnervation processes observed in ALS patients. In addition, fus loss of function alters tau transcripts favoring the expression of small tau isoforms. Overall, this new animal model extends our knowledge on FUS and supports the relevance of FUS loss of function in ALS physiopathology.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping