Type 1 Diabetes Prone NOD Mice Have Diminished <i>Cxcr1</i> mRNA Expression in Polymorphonuclear Neutrophils and CD4+ T Lymphocytes

<div><p>In humans, CXCR1 and CXCR2 are two homologous proteins that bind ELR+ chemokines. Both receptors play fundamental roles in neutrophil functions such as migration and reactive oxygen species production. Mouse <i>Cxcr1</i> and <i>Cxcr2</i> genes are located in an insulin-dependent diabetes genetic susceptibility locus. The non obese diabetic (NOD) mouse is a spontaneous well-described animal model for insulin-dependent type 1 diabetes. In this disease, insulin deficiency results from the destruction of insulin-producing beta cells by autoreactive T lymphocytes. This slow-progressing disease is dependent on both environmental and genetic factors. Here, we report descriptive data about the <i>Cxcr1</i> gene in NOD mice. We demonstrate decreased expression of mRNA for <i>Cxcr1</i> in neutrophils and CD4+ lymphocytes isolated from NOD mice compared to other strains, related to reduced NOD <i>Cxcr1</i> gene promoter activity. Looking for Cxcr1 protein, we next analyze the membrane proteome of murine neutrophils by mass spectrometry. Although Cxcr2 protein is clearly found in murine neutrophils, we did not find evidence of Cxcr1 peptides using this method. Nevertheless, in view of recently-published experimental data obtained in NOD mice, we argue for possible Cxcr1 involvement in type 1 diabetes pathogenesis.</p>