Homeostatic and Tissue Reparation Defaults in Mice Carrying Selective Genetic Invalidation of CXCL12/Proteoglycan Interactions

• DOI: 10.1161/circulationaha.112.113290
• Publication Date: 2012-10-04T03:40:50Z
• Authors: Patricia Rueda; Adèle Richart; Alice Récalde; Pamela Gasse; José Vilar; Coralie Guérin; Hugues Lortat-Jacob; Paulo Vieira; Frano̧ise Baleux; Fabrice Chretien; Fernando Arenzana...; Jean-Sébastien Si...
• Keywords: Homeostasis

Interaction with heparan sulfate proteoglycans is supposed to provide chemokines the capacity immobilize on cell surface and extracellular matrix for accomplishing both tissue homing signaling of attracted cells. However, consequences exclusive invalidation such interaction roles played by endogenous in vivo remain unascertained.We engineered a mouse carrying Cxcl12 gene (Cxcl12(Gagtm)) mutation that precludes interactions structures while not affecting CXCR4-dependent CXCL12 isoforms (α, β, γ). Cxcl12(Gagtm/Gagtm) mice develop normally, express normal levels total isoform-specific mRNA, show increased counting circulating CD34(+) hematopoietic precursor After induced acute ischemia, marked impaired support revascularization was observed animals associated reduced number infiltrating cells ischemic despite massive expression isoforms. Importantly, exogenous administration CXCL12γ, which binds highest affinity ever reported cytokine, fully restores vascular growth, whereas sulfate-binding CXCL12γ mutants failed promote animals.These findings prove role functions homeostasis physiopathological settings document first time paradigm chemokine immobilization vivo.