A Trem2^R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques.

ABSTRACT:

Background

The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer's Disease (AD). Unfortunately, many current Trem2 ^R47H mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2^{R47H NSS} (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products.

Methods

Trem2^{R47H NSS} mice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque dev

SUBMITTER: Tran KM 

PROVIDER: S-EPMC9938579 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature