Trem2 Splicing and Expression are Preserved in a Human Aβ-producing, Rat Knock-in Model of Trem2-R47H Alzheimer's Risk Variant.

ABSTRACT: The R47H variant of the Triggering-Receptor-Expressed on Myeloid cells 2 (TREM2) increases the risk of Alzheimer's disease (AD). Mutagenesis of exon 2 in Knock-in (KI) mouse models of the R47H variant introduced a cryptic splice site, leading to nonsense mediated decay. Since haploinsufficiency does not model Trem2-R47H function, a new rat KI model, the Trem2^R47H KI rat was created. Human Aβ has higher propensity to form toxic Aβ species, which are considered the main pathogenic entity in AD, as compared to rodent Aβ, the rat Amyloid Precursor Protein (App) gene was mutated to produce human Aβ. Trem2 splicing and expression was measured in Trem2^R47H KI rat brains and microglia by qualitative and quantitative RT-PCR. Trem2 levels and Trem2 processing was assessed by We

SUBMITTER: Tambini MD 

PROVIDER: S-EPMC7058057 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature