Figure 1.
Mice with inducible SBDS deficiency in hematopoietic and osteolineage niche cells develop disrupted hematopoiesis consistent with BM failure. (A) Mx1CreSbdsExc mice were generated by crossing Mx1Cre+ mice with Sbdsl/l mice to generate Mx1Cre+Sbdsl/l mice. Cre expression and Sbds deletion were induced in hematopoietic and Mx1-inducible niche cells by pIpC treatment to create Mx1Cre+SbdsExc mice. (B) After 4 weeks of pIpC treatment, qPCR demonstrated reduced Sbds mRNA expression in flushed BM cells compared with pIpC-treated Sbdsl/l controls. (C) Compared with pIpC-treated control Sbdsl/l mice (n = 7), Mx1CreSbdsExc 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 Mx1CreSbdsExc vs control mice after 4 weeks of pIpC treatment. (E) Mx1CreSbdsExc 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.

Mice with inducible SBDS deficiency in hematopoietic and osteolineage niche cells develop disrupted hematopoiesis consistent with BM failure. (A) Mx1CreSbdsExc mice were generated by crossing Mx1Cre+ mice with Sbdsl/l mice to generate Mx1Cre+Sbdsl/l mice. Cre expression and Sbds deletion were induced in hematopoietic and Mx1-inducible niche cells by pIpC treatment to create Mx1Cre+SbdsExc mice. (B) After 4 weeks of pIpC treatment, qPCR demonstrated reduced Sbds mRNA expression in flushed BM cells compared with pIpC-treated Sbdsl/l controls. (C) Compared with pIpC-treated control Sbdsl/l mice (n = 7), Mx1CreSbdsExc 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 Mx1CreSbdsExc vs control mice after 4 weeks of pIpC treatment. (E) Mx1CreSbdsExc 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.

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