Mice deficient in platelet-derived serotonin have reduced gap formation. (A) Serotonin concentrations were measured in whole blood from mast cell-deficient mice (Kit^W-sh), neutrophil-depleted mice, platelet-depleted mice, and their corresponding control mice using an ELISA serotonin kit. (B) Serotonin concentration was measured in platelet isolated from WT and Slc6a4^−/− mice. (C) WT and Slc6a4^−/− arthritic mice were injected intravenously with 0.45-μm-diameter fluorescent microsphere, and the fluorescence was visualized 5 minutes later using an in vivo imaging system. Control mice (WT nonarthritic) and WT and Slc6a4^−/− arthritic mice all received the same concentration of fluorescent microspheres. The radiant efficiency quantifications in the ankle joints for all mice are presented, and representative results are presented at right. ***P = .004. (D) Mice (17/group) sufficient and deficient in SERT expression were injected with 125 μL K/BxN serum at day 0 and day 2 and the signs of arthritis monitored daily. The mouse arthritis experiment is presented as mean ± SEM. P < .01. (E) SERT pharmacologic inhibition was performed in C57BL/6J mice by treating the mice with fluoxetine for 21 days before administration of K/BxN serum. Arthritic (treated or not with fluoxetine) and control (nonarthritic) mice were injected intravenously with 0.45-μm-diameter fluorescent microsphere, and the fluorescence was visualized 5 minutes later using an in vivo imaging system. The radiant efficiency quantifications in the ankle joints for all mice are presented, and representative results are presented at right. **P = .0092. (F) Serotonin concentrations in platelets isolated from mice treated or not with fluoxetine were measured by ELISA.