Figure 5.
Bcl-xL restrains Bak to inhibit platelet death. (A) Bak+/Q75L and BakQ75L/Q75L mice had significantly decreased platelet numbers compared with Bak+/+ mice. n = 20. (B) Platelets harboring the Q75L mutation have a reduced life span. n = 8 for BakQ75L/Q75L; n = 4 for Bak+/Q75L. t1/2 is indicated by a dotted line. Platelets from wild-type mice have a t1/2 of ∼5 d. n = 4. (C) The effect of the Q75L mutation on platelet numbers is not due to impaired megakaryopoiesis, as the number of mature megakaryocytes was elevated in both Bak+/Q75L and BakQ75L/Q75L mice compared with wild-type mice. n = 12. (D) Loss of Bax resulted in increased platelet counts in Bak+/Q75L and BakQ75L/Q75L mice. n = 3–8. (E) Loss of Bim has no effect on platelet levels in platelets harboring the Q75L mutation (n = 4–17), although loss of Bim alone resulted in thrombocytopaenenia, as previously observed. Data are presented as mean ± SEM. (****) P < 0.0001; (**) P < 0.01; (*) P < 0.05, Student's unpaired t-test.
