These TREM2-R47H mice carry a targeted mutation in which a Tet system controls the expression of human triggering receptor expressed on myeloid cells 2 (TREM2) containing the pathogenic R47H mutation with N-terminal HA and C-terminal 3xFLAG tags, and EGFP from the endogenous Gt(ROSA)26Sor promoter. An upstream floxed neo cassette blocks expression of tTA, tetO, and both TREM2-R47H and EGFP until Cre-mediated deletion. Trem2 encodes a protein that is part of a receptor signaling complex with TYRO protein tyrosine kinase binding protein (TYROBP2; DNAX Adaptor Protein 12, DAP12), and that activates microglia, macrophages, and dendritic cells during immune responses. Loss-of-function and sequence variations of the TREM2 gene in human populations indicate an essential function of microglia and innate immunity in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. The pathogenic R47H mutation has been shown to correlate with increased risk of late-onset Alzheimer's disease. Mice that are homozygous for the targeted mutation are viable, fertile and do not exhibit any abnormal phenotype. TREM2-R47H were bred to Cx3cr1CreER mice (Stock No. <a href="https://www.jax.org/strain/021160">021160</a>) to allow tamoxifen-induced, microglia-specific expression of human TREM2-R47H. When further bred to the 5xFAD amyloid mouse model (MMRRC No. 034848-JAX), resulting 5xFAD/TREM2-R47H mice exhibit exacerbated amyloid burden and related toxicity during the amyloid rapid growth period with the upregulated antigen presentation pathway in the microglia. The donating investigator reports no EGFP fluorescence prior to Cre recomination. After Cre recombination, EGFP can be detected by direct fluorescence. Additional administration of doxycycline blocks expression of TREM2-R47H and EGFP. Of note, TREM2-WT mice (Stock No. <a href="https://www.jax.org/strain/040009">040009</a>) express wildtype human TREM2-WT in the early amyloid seeding stage, but not during later stages of amyloid development, significantly reduced the amyloid deposition.

Use of MICE by companies or for-profit entities requires a license prior to shipping.

The expression of mutant human TREM2-R47H and EGFP in this TREM2-R47H strain can be engaged or disengaged in a temporal and tissue specific manner following cre-excision of a floxed stop cassette and doxycycline administration. This strain may be useful in studies of TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

<a target="_blank" href="https://www.jax.org/jax-mice-and-services/customer-support" rel="noreferrer">Contact Customer Service</a> for more information.