Figure 3. Platelet number and life span in Rasa3^hlb/hlb mice are normalized by reducing CalDAG-GEFI expression.

(A and B) Deletion of CalDAG-GEFI restores the peripheral platelet count and platelet life span in Rasa3^hlb/hlb mice. (A) Whole blood samples were obtained from controls and Caldaggef1^+/+ Rasa3^hlb/hlb, Caldaggef1^+/– Rasa3^hlb/hlb, and Caldaggef1^–/– Rasa3^hlb/hlb mice, and platelet counts per ml blood were determined (n = 6). (B) Whole blood samples were obtained from WT, Caldaggef1^+/+ Rasa3^hlb/hlb, Caldaggef1^+/– Rasa3^hlb/hlb, and Caldaggef1^–/– Rasa3^hlb/hlb mice at the indicated time points after injection of anti-GPIX Alexa Fluor 488, and the fraction of labeled to unlabeled platelets was determined (n = 6). *P < 0.05, ***P < 0.0001, 2-way ANOVA with Bonferroni post-test. (C) Reduced platelet half-life in Rasa3^hlb/hlb mice is caused by a defect that is intrinsic to platelets. The bar graph shows the survival of Caldaggef1^+/– Rasa3^+/+ or Caldaggef1^+/– Rasa3^hlb/hlb platelets after transfusion into WT recipient mice (n = 6). ***P < 0.0001, 2-tailed Student’s t test.