Use of a conditional Glanzmann thrombasthenia mouse model reveals a supportive and possibly non-adhesive role for TLT-1 in the platelet-fibrinogen interaction

The platelet integrin receptor, αIIbβ3, binds fibrinogen to mediate platelet-platelet contacts, regulate hemostasis, and modulate inflammation. The Triggering Receptor Expressed in Myeloid (TREM) - Like (TLT)-1 is an enigmatic 34kD receptor found on platelets that affects their hemostatic and inflammatory functions. Similar to αIIbβ3, TLT-1's ligand is also fibrinogen; however, TLT-1's direct role in platelet function remains unknown. We created a tamoxifen-inducible conditional αIIb deficient (<i>^cItga2b^-/-</i>) mouse to better understand TLT-1's role in platelet function, specifically TLT-1's binding to fibrinogen and its role in hemostasis and inflammation. We first characterized our <i>^cItga2b^-/-</i> null mouse and subsequently crossed this mouse with a Treml1^-/- mouse, creating a conditional double knockout (^cDKO). While the floxed <i>^cItga2b /Treml1^-/-</i> mouse shows significant differences compared to control mice, deleting Treml1 from the <i>^cItga2b^-/-</i> mouse results in only minor differences from the <i>^cItga2b^-/-</i> strain in bleeding, aggregation, fibrinogen deposition and platelet spreading assays. Our data suggest that while TLT-1 plays a visible role in hemostasis, it primarily supports aggregation but may not function as an adhesive component.