%0 Journal Article
%A Voigt, Aaron
%A Herholz, David
%A Fiesel, Fabienne C
%A Kaur, Kavita
%A Müller, Daniel
%A Karsten, Peter
%A Weber, Stephanie S
%A Kahle, Phillip
%A Marquardt, Till
%A Schulz, Jörg B
%T TDP-43-mediated neuron loss in vivo requires RNA-binding activity.
%J PLOS ONE
%V 5
%N 8
%@ 1932-6203
%C San Francisco, California, US
%I PLOS
%M DZNE-2020-02414
%P e12247
%D 2010
%X Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly linked to human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative impacts of TDP-43 alteration, mutation, or inherent protein function on neural integrity, however, remain less clear-a situation confounded by conflicting reports based on transient and/or random-insertion transgenic expression. We therefore performed a stringent comparative investigation of impacts of these TDP-43 modifications on neural integrity in vivo. To achieve this, we systematically screened ALS/FTLD-associated and synthetic TDP-43 isoforms via same-site gene insertion and neural expression in Drosophila; followed by transposon-based motor neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic approach we uncovered a requirement of inherent TDP-43 RNA-binding function-but not ALS/FTLD-linked mutation, mislocalization, or truncation-for TDP-43-mediated neurotoxicity in vivo.
%K Amyotrophic Lateral Sclerosis: genetics
%K Animals
%K Cell Line
%K Chickens: genetics
%K Chickens: metabolism
%K Chickens: physiology
%K DNA-Binding Proteins: genetics
%K DNA-Binding Proteins: metabolism
%K Drosophila melanogaster: cytology
%K Drosophila melanogaster: genetics
%K Drosophila melanogaster: metabolism
%K Drosophila melanogaster: physiology
%K Frontotemporal Lobar Degeneration: genetics
%K Gene Expression Regulation
%K Humans
%K Intracellular Space: metabolism
%K Locomotion
%K Longevity
%K Male
%K Motor Neurons: metabolism
%K Mutation
%K Neurons: cytology
%K Neurons: metabolism
%K Organ Specificity
%K Protein Binding
%K Protein Transport
%K RNA: metabolism
%K DNA-Binding Proteins (NLM Chemicals)
%K RNA (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:20806063
%2 pmc:PMC2923622
%R 10.1371/journal.pone.0012247
%U https://pub.dzne.de/record/136092