Table 2.

Effect of mutations in the CXCR2 and CXCR4 signaling systems.

Genotype	Phenotype
	Receptor Signaling	Early Mortality	Immune System	Cardiovascular Development	Cerebellar Development
Human CXCR4+/WHIM	Increased; impaired desensitization	0%	Panleukopenia Myelokathexis Low Igs Impaired vaccine responses Recurrent infections Persistent HPV disease HPV and EBV associated cancer	Tetralogy of Fallot (n=4)	Abnormal vermis (n=5)
Mouse Cxcr4+/WHIM	Increased; impaired desensitization	0%	Panleukopenia (B>T~N), reversed by AMD3100 No myelokathexis Normal Ig levels Low cellularity in spleen due to low B and T lymphocytes No spontaneous infections No warts or spontaneous cancers	na	na
Mouse Cxcr4+/o	Decreased	0%	normal	na	na
Mouse Cxcr4−/−	None	100%	Impaired BM myelopoiesis Impaired B cell lymphopoiesis Neutrophilia	VSD Abnormal gastric and renal vascularization	Disorganized granule cell layer
Mouse Cxcl2−/−	None	100%	Impaired BM myelopoiesis Impaired B cell lymphopoiesis	VSD Abnormal gastric and renal vascularization	Disorganized granule cell layer
Mouse Ackr3−/−	Impaired due to defective Cxcl12 gradient formation	70-95%	Impaired marginal zone B cell development	Cardiomegaly, VSD, semilunar valve atresia, lymphatic sac dilatation	Normal
Human CXCR2fs/fs	Absent CXCL2-dependent chemotaxis, ERK phosphorylation	0%	Myelokathexis	na	na
Mouse Cxcr2−/−	None	0%	Complete ko, SPF: neutrophilia, myeloid hyperplasia, extramedullary myelopoiesis Complete ko, GF: myeloid hyperplasia, normal ANC Mixed WT/ Cxcr2−/− bone marrow chimeras: Cxcr2−/− Myelokathexis	na	na

B, B cells; T, T cells; N, neutrophils; Ig, immunoglobulin; BM, bone marrow; VSD, ventricular septal defect; n, number of patients; na, not available/reported; SPF, specific pathogen-free; GF, germ-free; WT, wild type; ANC, absolute neutrophil count in blood