title: Functional defect of peripheral neutrophils in mice with induced deletion of CXCR2.
abstract: Type 2 CXC chemokine receptor CXCR2 plays roles in development, tumorigenesis, and inflammation. CXCR2 also promotes demyelination and decreases remyelination by actions toward hematopoietic cells and nonhematopoietic cells. Germline CXCR2 deficient (Cxcr2(-/-) ) mice reported in 1994 revealed the complexity of CXCR2 function and its differential expression in varied cell-types. Here, we describe Cxcr2(fl/fl) mice for which the targeting construct was generated by recombineering based on homologous recombination in E. coli. Without recombination Cxcr2(fl/fl) mice have CXCR2 expression on neutrophils in peripheral blood, bone marrow and spleen. Cxcr2(fl/fl) mice were crossed to Mx-Cre mice in which Cre recombinase is induced by Type I interferons, elicited by injection with polyinosinic-polycytidylic acid (poly(I:C)). CXCR2-deficient neutrophils were observed in poly(I:C) treated Cxcr2(fl/fl) ::Mx-Cre(+) (Cxcr2-CKO) mice, but not in poly(I:C) treated Cxcr2(f//+) ::Mx-Cre(+) mice. CXCR2 deletion was mainly observed peripherally but not in the CNS. Cxcr2-CKO mice showed impaired neutrophil migration in sterile peritonitis. Cxcr2-CKO mice reported here will provide a genetic reagent to dissect roles of CXCR2 in the neutrophil granulocyte lineage. Furthermore Cxcr2(fl/fl) mice will provide useful genetic models to evaluate CXCR2 function in varied cell populations.
authors: Department of Neuroscience, Neuroinflammation Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Liping
authors: L
authors: Liu
authors: MeiZhang
authors: M
authors: Li
authors: Lisa C
authors: LC
authors: Spangler
authors: Charles
authors: C
authors: Spear
authors: Mike
authors: M
authors: Veenstra
authors: Lindsey
authors: L
authors: Darnall
authors: Cathleen
authors: C
authors: Chang
authors: Anne C
authors: AC
authors: Cotleur
authors: Richard M
authors: RM
authors: Ransohoff
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D017353:Gene Deletion; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D023063:Receptors, Interleukin-8B / Q000235:genetics* / Q000378:metabolism
chemical_list: D023063:Receptors, Interleukin-8B
keywords: CXCR2; chemokine; chemokine receptor; conditional KO mice; neutrophil
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