Functional defect of peripheral neutrophils in mice with induced deletion of CXCR2. Issue 8 (24th June 2013)

• Record Type: Journal Article
• Authors: Liu, LiPing; Li, MeiZhang; Spangler, Lisa C.; Spear, Charles; Veenstra, Mike; Darnall, Lindsey; Chang, Cathleen; Cotleur, Anne C.; Ransohoff, Richard M.
• Is Part Of: Genesis. Volume 51:Issue 8(2013:Aug.)
• Page Start: 587
• Page End: 595
• Publication Date: 2013-06-24
• Subjects: Developmental genetics -- Periodicals; Genetics -- Periodicals; Developmental biology -- Periodicals; Embryology -- Periodicals; Genetic regulation -- Periodicals; 576.5
• DOI: 10.1002/dvg.22401
• Languages: English
• ISSNs: 1526-954X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 (<italic>Cxcr</italic>2<sup><italic>‐/‐</italic></sup>) mice reported in 1994 revealed the complexity of CXCR2 function and its differential expression in varied cell‐types. Here, we describe <italic>Cxcr</italic>2<sup><italic>fl/fl</italic></sup> mice for which the targeting construct was generated by recombineering based on homologous recombination in <italic>E. coli</italic>. Without recombination <italic>Cxcr</italic>2<sup><italic>fl/fl</italic></sup> mice have CXCR2 expression on neutrophils in peripheral blood, bone marrow and spleen. <italic>Cxcr</italic>2<sup><italic>fl/fl</italic></sup> mice were crossed to <italic>Mx‐Cre</italic> 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 <italic>Cxcr2<sup>fl/fl</sup>::Mx‐Cre<sup>+</sup></italic> (<italic>Cxcr</italic>2‐CKO) mice, but not in poly(I:C) treated <italic>Cxcr2<sup>f//+</sup>::Mx‐Cre<sup>+</sup></italic> mice. CXCR2 deletion was mainly observed peripherally but not in the CNS. <italic>Cxcr</italic>2‐CKO mice showed impaired neutrophil migration in sterile peritonitis. <italic>Cxcr</italic>2‐CKO mice reported here will provide a genetic reagent to dissect roles of CXCR2 in the neutrophil granulocyte lineage. Furthermore <italic>Cxcr</italic>2<sup><italic>fl/fl</italic></sup> mice will provide useful genetic models to evaluate CXCR2 function in varied cell populations. genesis 51:587–595. © 2013 Wiley Periodicals, Inc.</p> </abstract>