Transgenic HoxB5 conditional DTR (cDTR) mice have been generated using CRISPR mediated targeting of the HoxB5 gene (exon2) in fertilized wildtype C57Bl/6 eggs that were then microinjected into pseudopregnant wildtype female mice. The construct targeted under the controls of the endogenous HoxB5 promoter consisted of the following elements: TagRFP (flanked by P2A sequences), Translational STOP (flanked by loxP sites) and a DTRGFP fusion protein.The HoxB5 cDTR mice therefore represent a unique tool to study the role of hematopoietic stem cells in health and disease.