VavCreBaxBakBid TKO mice die of BMF. (A) Schematic of hematopoietic homeostasis and BMF and development of VavCre transgenic mouse models to study the role of cell death. (B) Deletion of Bax in bone marrow and spleen determined by reverse-transcription polymerase chain reaction (top), and diagram of highlighting Cre-Lox recombination with loxP sites flanking exons 2 to 4 of the Bax gene (bottom). (C) Immunoblot examining the expression of Bax, Bak, and Bid in WT (Bid^+/+), VavCreBaxBak (DKO), and VavCreBaxBakBid (TKO) mice. (D) Survival curves of Bid^+/+, Bid^−/−, DKO, and TKO mice. Statistics demonstrate differences between DKO and TKO animals. Bid^+/+ n = 4, Bid^−/− n = 4, DKO n = 14, TKO n = 22. (E) Cause of death in DKO and TKO mice determined at time of necropsy. (F) Bone marrow and cerebrospinal fluid from Bid^+/+ mice transplanted with leukemic DKO bone marrow after sublethal irradiation. Arrows indicate leukemic blasts. Scale bar, 50 μm. (G) Complete blood counts, including RBCs (top; 10⁶/µL), platelet counts (middle; 10⁶/µL), and hemoglobin (bottom; g/dL); n = 3 and 4 Bid^+/+ and TKO mice, respectively. (H) Cytospins from bone marrow Bid^+/+ and TKO mouse bone marrow mice denoting neutrophils (I), megakaryocytes (II), and erythroid precursors (III). Arrows indicate hypersegmentation (I), hypolobulation (II), and binucleation and intrachromosomal bridging (III). Scale bars, 10 μm. *P < .05, ***P < .001. Data represent mean ± standard error of the mean (SEM). LDP, lymphoproliferative disorder.