Trem2
R47H NSS; 5xFAD mice display age/disease progression‐dependent changes in plaques and plaque‐associated microglia, and increased plasma neurofilament light chain

Genome‐Wide Association Studies revealed Triggering receptor expressed on myeloid cells 2 (TREM2) R47H mutation as one of the strongest genetic risk factors for late‐onset Alzheimer’s Disease (AD). In the brain, TREM2 is a transmembrane receptor expressed exclusively by myeloid cells. Many current TREM2*R47H mouse models have observed evidence of cryptic splicing products of the mutant allele, resulting in artefactually reduced protein product. Model Organism Development & Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) consortium at University of California ‐ Irvine has developed the Trem2 R47H NSS (Normal Splice Site) mouse model where the Trem2 allele is expressed at a level similar to the wild‐type Trem2 allele, with no evidence of cryptic splicing products from the mutant allele.