Neuronal overexpression of hTDP-43 in Caenorhabditis elegans impairs motor function

MicroPubl Biol. 2023 Apr 19:2023:10.17912/micropub.biology.000768. doi: 10.17912/micropub.biology.000768. eCollection 2023.

Abstract

Transactive response DNA binding-protein 43 (TDP-43) is a conserved RNA/DNA-binding protein with a role in RNA metabolism and homeostasis. Aberrant TDP-43 functioning has been considered a major culprit in amyotrophic lateral sclerosis (ALS). Caenorhabditis elegans can be used to phenocopy ALS in vivo . Since disrupted locomotion is a strong readout of toxicity, we examined multiple motor phenotypes of a C. elegans model expressing human wild-type TDP-43 ( hTDP-43 ) pan-neuronally. Our data reveal that impaired locomotion includes more than the common deficits in crawling capacity and the presence of early-onset paralysis. We show that reduced thrashing, abnormal coiling, and decreased pharyngeal pumping are also observed, in a temperature-dependent fashion.

Grants and funding

This project was funded by a BCN-Brain grant (to M.K.) and a grant of Stichting ALS Nederland (686990) (to E.A.A.N. and M.K.)