Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay.

ABSTRACT: Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. Here, we generated and characterized Grn^R493X knockin mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous Grn^R493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, cytoplasmic TDP-43 accumulation, reduced synaptic density, lipofuscinosis, hyperinflammatory macr

SUBMITTER: Nguyen AD 

PROVIDER: S-EPMC5866607 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature