PUBLICATION
Modeling sacsin depletion in Danio Rerio offers new insight on retinal defects in ARSACS
- Authors
- Naef, V., Damiani, D., Licitra, R., Marchese, M., Vecchia, S.D., Baggiani, M., Brogi, L., Galatolo, D., Landi, S., Santorelli, F.M.
- ID
- ZDB-PUB-250109-210
- Date
- 2025
- Source
- Neurobiology of disease : 106793106793 (Journal)
- Registered Authors
- Naef, Valentina, Santorelli, Filippo Maria
- Keywords
- ARSACS, Neurological disorder, Retina development, Retinal abnormalities, Zebrafish
- MeSH Terms
-
- Zebrafish*
- Animals
- Heat-Shock Proteins/genetics
- Heat-Shock Proteins/metabolism
- Disease Models, Animal*
- Retinal Degeneration/genetics
- Retinal Degeneration/metabolism
- Retinal Degeneration/pathology
- Spinocerebellar Ataxias*/congenital
- Spinocerebellar Ataxias*/genetics
- Spinocerebellar Ataxias*/pathology
- Muscle Spasticity*/genetics
- Animals, Genetically Modified
- Retina*/metabolism
- Retina*/pathology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 39778749 Full text @ Neurobiol. Dis.
Citation
Naef, V., Damiani, D., Licitra, R., Marchese, M., Vecchia, S.D., Baggiani, M., Brogi, L., Galatolo, D., Landi, S., Santorelli, F.M. (2025) Modeling sacsin depletion in Danio Rerio offers new insight on retinal defects in ARSACS. Neurobiology of disease. :106793106793.
Abstract
Biallelic mutations in the SACS gene, encoding sacsin, cause early-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disease also characterized by unique and poorly understood retinal abnormalities. While two murine models replicate the phenotypic and neuronal features observed in patients, no retinal phenotype has been described so far. In a zebrafish knock-out strain that faithfully mirrors the main aspects of ARSACS, we observed impaired visual function due to photoreceptor degeneration, likely caused by cell cycle defects in progenitor cells. RNA-seq analysis in embryos revealed dysfunction in proteins related to fat-soluble vitamins (e.g., TTPA, RDH5, VKORC) and suggested a key role of neuroinflammation in driving the retinal defects. Our findings indicate that studying retinal pathology in ARSACS could be crucial for understanding the impact of sacsin depletion and may offer insights into halting disease progression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping