Functional defect of peripheral neutrophils in mice with induced deletion of CXCR2

Genesis. 2013 Aug;51(8):587-95. doi: 10.1002/dvg.22401. Epub 2013 Jun 24.

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.

Keywords: CXCR2; chemokine; chemokine receptor; conditional KO mice; neutrophil.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Gene Deletion*
  • Mice
  • Mice, Knockout
  • Neutrophils / metabolism*
  • Neutrophils / physiology
  • Receptors, Interleukin-8B / genetics*
  • Receptors, Interleukin-8B / metabolism

Substances

  • Receptors, Interleukin-8B