P47(phox)-deficient NADPH oxidase defect in neutrophils of diabetic mouse strains, C57BL6/J-m db/db and db/+

Deficiencies in neutrophil NADPH oxidase proteins have been demonstrated in humans with chronic granulomatous disease. However, no spontaneous mutatio n in murine NADPH oxidase has been reported. In this study we report that n eutrophils from the diabetic mouse strains, C57BL/6J-m heterozygous lean (l epr(db/+)) and homozygous obese (lepr(db/db)) mice produced no superoxide o n stimulation. An absence of intact p47(phox) but not other oxidase protein s was ol,served in both mouse strains through the use of inmunoblotting. Mo lecular analysis by reverse transcriptase-polymerase chain reaction identif ied three abnormal p47 phox mRNA transcripts. Sequencing of genomic DNA of p47(phox) revealed a point mutation at the -2 position of exon 8, which is consistent with aberrant splicing of the p47(phox) transcript. These result s indicate that the C57BL/6J-m db/db and db/+ mice are the first spontaneou sly derived murine model of NADPH oxidase deficiency involving a p47(phox) mutation.