PB0405 - Characterization of TLT-1 and P-selectin double null mouse in hemostatic and immune function

Background: Platelets play a key role in hemostasis and immune function. While hemostasis is well described, mechanisms underlying the platelet’s immunological function need to be elucidated. TREM-like transcript-1 (TLT-1) and P-selectin are both found in platelet alpha -granules and seem to affect leukocytes. P-selectin mediates initial leukocyte interactions and TLT-1 seems to be important for release before leukocyte transmigration. Loss of TLT-1 or P-selectin causes platelet altered hemostatic and immune functionality. To better understand this relationship, deficient TLT-1 and P-selectin (PT-DKO) mice were created to characterize their functionality.

Aims: Assess the hemostatic and immune functionality in TLT-1/P-selectin single and double KO.

Methods: Treml1-/- and Selp-/- mice were intercrossed on a C57BL/6J background to generate the treml1/Selp double null mouse (PT-DKO). They were backcrossed for 10 generations and the progeny of these mice were used in our study. Bleeding time, hemoglobin assay, aggregometry, lung injury, and flow cytometry were used to evaluate the hematological parameters in our mice.

Results: Our preliminary data show treml1-/- mice and Selp-/- had significant differences in bleeding time and hemoglobin assay, compared to WT. There was not a significant difference between WT and PT-DKO (Fig. 1). Platelet spreading to fibrinogen was found significantly decreased in PT-DKO compared to WT

Conclusion(s): This study is to characterize the hemostatic phenotype of a new mouse line to better understand the possible interaction between TLT-1 and P-selectin. Our findings in PT-DKO mice suggest a rescued hemostatic function comparable to WT mice. However, the platelet’s capability to bind fibrinogen seems to decrease. In bleeding assays, PT-DKO mice phenocopy WT phenotype mice and needs to be studied further with more emphasis on thrombotic events and inflammatory response. The current state of this project will be presented in this poster.