Deletion of the murine Duffy gene (Dfy) reveals that the duffy receptor isfunctionally redundant

All of the antigenic determinants of the Duffy blood group system are in a glycoprotein (gp-Fy), which is encoded by a single-copy gene (FY) located o n chromosome 1. gp-Fy is also produced in several cell types, including end othelial cells of capillary and postcapillary venules, the epithelial cell of kidney collecting ducts, lung alveoli, and the Purkinje cells of the cer ebellum. This protein, which spans the cell membrane seven times, is a memb er of the superfamily of chemokine receptors and a malarial parasite recept or. The mouse Duffy gene (Dfy) homolog of human FY is also a single-copy ge ne, which maps in a region of conserved synteny with FY and produces a glyc oprotein with 60% homology to the human protein. The mouse Duffy-like prote in also binds chemokines, To study the biological role of gp-Fy, we generat ed a mouse strain in which Dfy was deleted. These homozygous Dfy(-/-) mice were indistinguishable in size, development, and health from wild-type and heterozygous littermates. We also examined components of the immune system and found no differences in lymph nodes or peripheral blood leukocyte level s between knockout and wild-type mice. The gross and histological anatomy o f the thymus, spleen, lung, and brain showed no significant differences bet ween mutants and wild-type mice. There was no indication of an overall diff erence between the knockout and wild-type mice in systematic neurological e xaminations. The only significant difference between Dfy(-/-) and Dfy(+/+) mice that we found was in neutrophil migration in peritoneal inflammations induced by lipopolysaccharide and thioglycolate. In mice homozygous for the deletion, there was less neutrophil recruitment into the peritoneal cavity and neutrophil influx in the intestines and lungs than in wild-type mice. Despite this, the susceptibility to Staphylococcus aureus infection was the same in the absence and in the presence of gp-Fy. Our results indicate tha t gp-Fy is functionally a redundant protein that may participate in the neu trophil migratory process.