Trem2 Conditional Knockout mouse models

Trem2 is the mouse ortholog of human TREM2 and encodes a single immunoglobulin domain innate receptor on microglia and other myeloid cells that lacks its own signaling motifs and instead pairs with Tyrobp, also called DAP12, to trigger Syk, PI3K and PLC gamma signaling after binding anionic lipids, apolipoprotein E and amyloid beta, licensing the disease-associated microglial state, phagocytosis and plaque compaction. ADAM10 and ADAM17 shed the ectodomain to produce soluble TREM2, an established cerebrospinal fluid biomarker whose signaling role is distinct from the membrane receptor. Allele choice here is unusually consequential because the R47H Alzheimer risk variant introduced into mouse Trem2 created a cryptic splice site that lowered transcript and confounded early reports, so humanized TREM2 knockins carrying the human sequence are required for variant modeling. Conditional nulls with microglia-restricted inducible Cre address adult requirement. Read plaque-associated microglial coverage, transcriptional signatures, and shed ectodomain levels.

Trem2 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.