Inducible expression of human C9ORF72 36x G₄C₂ hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice.

ABSTRACT: The hexanucleotide G₄C₂ repeat expansion in the first intron of the C9ORF72 gene explains the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs) which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansion and accumulate in the brain of C9FTD/ALS patients. Mouse models expressing the human C9ORF72 repeat and/or DPRs show variable pathological, functional, and behavioral characteristics of FTD and ALS. Here, we report a new Tet-on inducible mouse model that expresses 36x pure G₄C₂ repeats with 100bp upstream and downstream human flanking regions. Brain specific expression causes the formation

SUBMITTER: Riemslagh FW 

PROVIDER: S-EPMC7903916 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature