The protein encoded by the triggering receptor expressed on myeloid cells 2 (TREM2) gene can form a receptor signaling complex with TYRO protein tyrosine kinase-binding protein. This protein is mainly expressed in macrophages and dendritic cells, among which microglia in the central nervous system are the core cell types for its expression. The TREM2 protein binds to the adapter protein Dap-12, recruits various signaling molecules such as kinases and phospholipase C-γ, and assembles to form a receptor signaling complex, thereby activating myeloid cells such as microglia and dendritic cells. Functionally, TREM2 participates in innate and adaptive immune responses, regulates the chronic inflammatory process by inducing the production of inflammatory cytokines, and it has been confirmed to be associated with colonic wound healing ^[1]. Genetic studies have shown that mutations in the TREM2 gene are one of the pathogenic factors for polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), and variations in this gene are closely related to an increased risk of neurodegenerative diseases such as Alzheimer's disease (AD) ^[2]. Tumor-associated macrophages (TAMs) are involved in the tumor's resistance to the immune system, and TREM2 plays a role in TAMs and myeloid-derived suppressor cells (MDSCs), with its expression level being positively correlated with tumor progression ^[3].

The B6-huTREM2 mouse is a humanized model constructed by gene-editing technology, in which the sequence from the upstream of exon 1 to the downstream of exon 5 of the mouse Trem2 gene is replaced with the corresponding sequence of the human TREM2 gene. This model can be used for the research of the pathological mechanisms of Alzheimer's disease (AD), polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), and some cancers, as well as the development of relevant treatment methods, and the screening, development, and pre-clinical evaluation of TREM2-targeted drugs.