Trem2^R47H and reduced <i>TREM2</i> expression both mimic human Alzheimer's disease signatures in mice.

ABSTRACT:

Introduction

TREM2 loss of function variants are associated with late-onset Alzheimer's disease (LOAD). We molecularly assessed mice with the missense variant, R47H (Trem2*R47H^HSS), and mice with additional cryptic splicing and reduced Trem2 expression (Trem2*R47H) while comparing relevance to human LOAD.

Methods

The aberrant splice acceptor site in the Trem2*R47H mouse was humanized resulting in the Trem2*R47H humanized splice site (Trem2*R47H^HSS) mouse. RNA sequencing was performed on mouse brain tissue and signatures were compared to human postmortem brain expression in LOAD cohorts.

Results

Trem2*R47H mice had alternative splicing leading to reduced Trem2 expression; Trem2*R47H^HSS mice expressed Trem2 at

SUBMITTER: Abel TR 

PROVIDER: S-EPMC12724514 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature