Figure 1.

Mice with inducible SBDS deficiency in hematopoietic and osteolineage niche cells develop disrupted hematopoiesis consistent with BM failure. (A) Mx1^CreSbds^Exc mice were generated by crossing Mx1^Cre+ mice with Sbds^l/l mice to generate Mx1^Cre+Sbds^l/l mice. Cre expression and Sbds deletion were induced in hematopoietic and Mx1-inducible niche cells by pIpC treatment to create Mx1^Cre+Sbds^Exc mice. (B) After 4 weeks of pIpC treatment, qPCR demonstrated reduced Sbds mRNA expression in flushed BM cells compared with pIpC-treated Sbds^l/l controls. (C) Compared with pIpC-treated control Sbds^l/l mice (n = 7), Mx1^CreSbds^Exc mice (n = 12) developed reduced platelet counts and an increased peripheral blood myeloid/lymphoid (M/L) cell ratio, consistent with stress hematopoiesis. (D) Representative dot plots showing decreased percentages of lin^-Sca1⁺cKit⁺ (LSK) cells and CD48^-CD150⁺ long-term HSC (LT-HSC) in total BM of Mx1^CreSbds^Exc vs control mice after 4 weeks of pIpC treatment. (E) Mx1^CreSbds^Exc BM (n = 2) shows severe reduction in percentages of LSK and LT-HSC compared with control BM (n = 4). *P < .05; ***P < .001; Student t test.