TBK1 is involved in programmed cell death and ALS-related pathways in novel zebrafish models.

ABSTRACT: Pathogenic mutations within the TBK1 gene leading to haploinsufficiency are causative of amyotrophic lateral sclerosis (ALS). This gene is linked to autophagy and inflammation, two cellular mechanisms reported to be dysregulated in ALS patients, although its functional role in the pathogenesis could involve other players. We targeted the TBK1 ortholog in zebrafish, an optimal vertebrate model for investigating genetic defects in neurological disorders. We generated zebrafish models with invalidating tbk1 mutations using CRISPR-Cas9 or tbk1 knockdown models using antisense morpholino oligonucleotide (AMO). The early motor phenotype of zebrafish injected with tbk1 AMO beginning at 2 days post fertilization (dpf) is associated with the degeneration of motor neurons. In parallel, CRISPR-induce

SUBMITTER: Raas Q 

PROVIDER: S-EPMC11903655 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature