ARHGAP25 deficiency in HSPCs leads to defects in mobilization.Arhgap25^−/− mice, obtained from KOMP, were confirmed at the DNA and protein level to be deficient in ARHGAP25 protein (not shown). (A) Mice lacking ARHGAP25 had significantly higher percentages of LSK HSPCs in their BM than controls (left), and lower proportions of HSPCs in their peripheral blood (center), suggesting increased central compartmentalization. This continued to be true after mobilization with Cy/G (right), indicating that ARHGAP25 is required for optimal mobilization. Each dot represents an individual mouse. (B) To confirm that this finding is due to intrinsic activity of ARHGAP25 in hematopoietic cells, Arhgap25^−/− BM was transplanted into lethally irradiated recipient mice. After 16 weeks of hematopoietic reconstitution, recipients of Arhgap25^−/− marrow were found to have increased percentages of LSK cells in the BM (left) and decreased percentages in the peripheral blood (center), demonstrating that ARHGAP25 function is intrinsic to the hematopoietic system in this context. After Cy/G treatment, diminished mobilization was again seen in recipients of Arhgap25^−/− marrow as compared with controls (right). These differences did not reach statistical significance, however, in part because recipients of control marrow reproducibly mobilized far less well than unmanipulated WT mice. Each dot represents an individual mouse. ctrl, control.