Characterization of a C9orf72 Knockout Danio rerio model for ALS and cross-species validation of potential therapeutics screened in Caenorhabditis elegans - PubMed
3 hours ago
- #C9orf72 knockout
- #ALS
- #therapeutic screening
- A zebrafish C9orf72 knockout model was created using CRISPR/Cas9 to study ALS, showing dose-dependent increased larval mortality, growth reduction, and motor deficits.
- Homozygous C9orf72 loss-of-function larvae exhibited mild overbranching of spinal motoneurons, providing insights into neurodegenerative mechanisms.
- A screen in a C. elegans C9orf72 homolog model identified 12 compounds that improved motility and reduced neurodegeneration, with two tested in zebrafish.
- Pizotifen malate significantly improved motor deficits in the zebrafish C9orf72 knockout model, highlighting it as a promising therapeutic candidate for further evaluation.
- The model offers a valuable tool for in vivo C9orf72 research and cross-species validation of potential ALS therapeutics, differing from previous depletion models.