The Trem2 gene encodes the triggering receptor expressed on myeloid cells-2 (TREM2), a transmembrane protein produced by microglia in the brain, primarily regulating the survival and activation of these cells. This protein forms a receptor signaling complex by binding to the adaptor protein Dap-12 and recruiting various factors such as kinases and phospholipase C-γ, thereby activating myeloid cells, including dendritic cells and microglia. Mutations in the Trem2 gene are associated with neurodegenerative diseases, metabolic syndrome, and cancer. Research has found that the absence of the Trem2 gene leads to the onset of Nasu-Hakola disease (also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy), a rare autosomal recessive genetic disease characterized by fractures and early-onset frontotemporal dementia. In addition, certain variants may increase the risk of Alzheimer’s disease (AD) and other neurodegenerative diseases.

This strain is a mouse model with the Trem2 gene knocked out, which can be used to study the biological consequences of TREM2 functional loss. It can also be crossed with transgenic mice related to APP and tau proteins to study the impact of TREM2 functional loss in the context of amyloid degeneration and tau pathology. Homozygous Trem2 KO mice are viable and fertile.