Feasibility of an allele-nonselective Cxcr4 inactivation cure strategy for WHIM syndrome. (A) Possible gene-editing cure strategies for the gain-of-function mutations causing WHIM syndrome. ∗ denotes WHIM mutation location in Cxcr4. (B) The 4 possible genotypes produced by allele-nonselective Cxcr4 inactivation. (C) Absolute leukocyte subtype counts in mouse blood stratified by Cxcr4 genotype. N > 19 mice in each group. (D-E) Hematopoietic reconstituting activity of Cxcr4^o/w vs Cxcr4^+/w BM cells during competitive transplantation of lethally irradiated Cxcr4^+/w recipient mice (D) and after single genotype BM transplantation of unconditioned Cxcr4^+/w recipient mice (E). The experimental schemes are shown at the top of panels D and E. Donor and recipient cells were marked by different CD45 isoforms for detection and quantitation via flow cytometry. n = 5 mice in each group in panels D and E. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. Data in panels D and E are from a single experiment and are representative of 2 experiments for panel D.