A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in a AAV-C9ORF72 (G₄C₂)₆₆ mouse model.

ABSTRACT: The G₄C₂ hexanucleotide repeat expansion in C9ORF72 is the major genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Despite considerable efforts, the development of mouse models of C9-ALS/FTD useful for therapeutic development has proven challenging due to the intricate interplay of genetic and molecular factors underlying this neurodegenerative disorder, in addition to species differences. This study presents a robust investigation of the cellular pathophysiology and behavioral outcomes in a previously described AAV mouse model of C9-ALS expressing 66 G₄C₂ hexanucleotide repeats. Despite displaying key molecular ALS pathological markers including RNA foci, dipeptide repeat (DPR) prote

SUBMITTER: Thompson EG 

PROVIDER: S-EPMC11383318 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature