TARDBP (TDP-43) Knock-in Zebrafish Display a Late-Onset Motor Phenotype and Loss of Large Spinal Cord Motor Neurons.

ABSTRACT:

Objective

Mutations in TARDBP (encoding TDP-43) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and include familial missense mutations where there are a lack of models and mechanisms examining how they are pathogenic.

Methods

In this study, we developed 2 tardbp (Tdp-43) knock-in (KI) zebrafish mutant models encoding the analogous A382T and G348C variants and investigated their degenerative phenotypes.

Results

We show that both models display reduced survival as well as an age-dependent motor phenotype that manifests at 1.5 years. Both variants in either the heterozygous or homozygous state did not impact protein expression levels of Tdp-43 in the central nervous system. However, homozygous G347C zebrafish displayed reduced expre

SUBMITTER: Harji ZA 

PROVIDER: S-EPMC12946615 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature