English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Mutations in the transactive response DNA binding protein-43 ( TARDBP/TDP-43)  gene, which regulates transcription and splicing, causes a familial form of amyotrophic lateral sclerosis (ALS). Here, we characterize and report the first  tardbp  mutation in zebrafish, which introduces a premature stop codon (Y220X), eliminating expression of the Tardbp protein. Another  TARDBP  ortholog,  tardbpl , in zebrafish is shown to encode a Tardbp-like protein which is truncated compared with Tardbp itself and lacks part of the C-terminal glycine-rich domain (GRD). Here, we show that  tardbp  mutation leads to the generation of a novel  tardbpl  splice form ( tardbpl-FL ) capable of making a full-length Tardbp protein (Tardbpl-FL), which compensates for the loss of Tardbp. This finding provides a novel  in vivo  model to study TDP-43-mediated splicing regulation. Additionally, we show that elimination of both zebrafish  TARDBP  orthologs results in a severe motor phenotype with shortened motor axons, locomotion defects and death at around 10 days post fertilization. The Tardbp/Tardbpl knockout model generated in this study provides an excellent  in vivo  system to study the role of the functional loss of Tardbp and its involvement in ALS pathogenesis.

Tardbpl splicing rescues motor neuron and axonal development in a mutant tardbp zebrafish