Document Type

Article

Publication Date

11-11-2023

Comments

This article is the author's final published version in International Journal of Molecular Sciences, Volume 24, Issue 22, November 2023, Article number 16214.

The published version is available at https://doi.org/10.3390/ijms242216214.

Copyright © 2023 by the authors

Abstract

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. It is reasonable to infer that an amplification of an as-yet undetermined hnRNPA1 function plays a pivotal role in the pathogenesis of familial ALS caused by pathogenic hnRNPA1 mutation.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

38003404

Language

English

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