Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We wished to determine when each of the four NADPH oxidase components p22 phagocytic oxidase (phox), gp91 phox, p47 phox, p67 phox is first expressed embryologically and whether the expression pattern occurs in a consistent temporal sequence or whether the four genes are expressed simultaneously. A deficiency of any one of them results in chronic granulomatous disease (CGD). mRNA transcripts and protein expression for p22 phox, gp91 phox, p47 phox, p67 phox was monitored in murine embryos at time of implantation (E5.5) until E 11.5, and in fetal liver, spleen, and limb bone marrow from E 14 until term (E 19). We observed that mRNA was first expressed for p22 phox at E 5.5, for p67 phox at E 7.0 and for p47 phox at E 7.5 before the onset of yolk sac hematopoiesis (E 8.0). gp91 Phox mRNA was first expressed at E 9.0. However, only p22 phox protein was expressed in circulating hemocytoblast by E 9.0. No other embryonic tissue contained phox proteins either before or after the establishment of hemocytoblastic circulation. The four specific mRNA transcripts and phox proteins were expressed in nests of developing granulocytes in liver by E 14 and the expression continued in the liver at E 16 and E 19. Spleen and limb bone marrow showed inconsistent results. Cord blood neutrophils contained all phox proteins. These studies confirm that the four CGD-related phox mRNA components of NADPH oxidase are expressed early in embryonic development and the expression occurs in a consistent sequential fashion but only p22 phox protein appears in embryonic hemocytoblast.
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PMID:Developmental expression of NADPH phagocytic oxidase components in mouse embryos. 1044 7

A recessive Salmonella Typhimurium susceptibility locus (immunity to Typhimurium (Ity3) was reported previously on distal mouse chromosome 1 using a cross between C57BL/6J and wild-derived MOLF/Ei mice. This quantitative trait locus is located in a genomic region spanning 84 Mb, rich in candidate genes for which a role in host resistance to Salmonella infection is either known or can be envisioned. In this study, we report the evaluation of neutrophil cytosolic factor 2 (Ncf2) as a candidate Salmonella susceptibility gene for Ity3. Ncf2 encodes p67phox, a subunit of the multiprotein enzyme complex NADPH oxidase, known to be responsible for the generation of superoxides. Congenic mice carrying the Ity3 region from MOLF/Ei, B6.MOLF-Ity/Ity3 were more susceptible to infection compared with control mice heterozygous at Ity3, B6.MOLF-Ity/Ity3(MOLF/B6), confirming the existence of a recessive Salmonella susceptibility locus on distal chromosome 1. Spleen Ncf2 expression levels were lower in infected congenic mice homozygous for the MOLF/Ei allele at Ity3 compared with mice heterozygous at Ity3. C57BL/6J and MOLF/Ei Ncf2 sequence comparisons revealed one nonconservative amino acid change (R394Q) in the functional and highly conserved Phox and Bem1 domain of the protein. Functional analysis revealed that the MOLF/Ei allele had reduced PMA- and Salmonella-induced superoxide induction as compared with their wild-type counterparts ex vivo. The R394Q substitution seems to occur on an amino acid involved in electrostatic interactions with p40phox, crucial in its activation. Moreover, a human mutation in the corresponding R395W, resulting in chronic granulatomous disease, is known to lead to reduced superoxide levels. These results support the candidacy of Ncf2 as the gene underlying Ity3.
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PMID:Sequencing, expression, and functional analyses support the candidacy of Ncf2 in susceptibility to Salmonella typhimurium infection in wild-derived mice. 1670 56