Neuronal Expression of UBQLN2^P497H Exacerbates TDP-43 Pathology in TDP-43^G348C Mice through Interaction with Ubiquitin.

ABSTRACT: Mutations in the gene encoding ubiquilin-2 (UBQLN2) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). UBQLN2 plays a central role in ubiquitin proteasome system (UPS) and UBQLN2 up-regulation exacerbates TDP-43 cytoplasmic aggregates. To analyze interaction between UBQLN2 and TDP-43 and to produce a relevant ALS animal model, we have generated a new transgenic mouse expressing UBQLN2^P497H under the neurofilament heavy (NFH) gene promoter. The UBQLN2^P497H mice were then bred with our previously described TDP-43^G348C mice to generate double-transgenic UBQLN2^P497H; TDP-43^G348C mice. With low-expression levels of UBQLN2, the double-transgenic mice developed TDP-43 cytosolic accumulations in motor neurons

SUBMITTER: Picher-Martel V 

PROVIDER: S-EPMC6647471 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature