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.

The TGA stop codon of the mouse Trem2 gene is replaced by P2A-Cre-WPRE. This model expresses Cre recombinase driven by the regulatory elements of the mouse Trem2 gene.

The “Mouse Trem2 promoter-Kozak-iCre-WPRE-BGH pA” cassette was inserted into H11 locus (5' of Eif4enif1 gene and 3' of the Drg1 gene). Cre recombinase is expressed under the regulatory control of Trem2 promoter.

The “IRES-CreERT2” cassette was inserted downstream of the TGA stop codon. CreERT2 recombinase is expressed under the regulatory control of Trem2 gene elements. This model is a Tamoxifen-inducible Cre mouse, and when crossed with mice containing loxP sites, the offspring mice are expected to undergo sequence recombination between loxP sites mediated by Cre recombinase in Trem2-positive cells following Tamoxifen induction.

Trem2 is located on chromosome 17 of mice. Nuclease Technology was used to design sgRNA; Trem2 knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.

Trem2 is located on chromosome 17 of mice. SgRNA and ssDNA were designed using Nuclease Technology; Trem2 conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.