Nucleobindin(Nuc) first identified in the supernatant of a lymphoid cell line of MRL/lpr mouse origin as an anti-DNA antibody boosting factor. Molecular cloning have revealed that Nuc has intriguing features such as a signal peptide, a leucine zipper, EF-hands and a nuclear localization signal. In vivo administration of recombinant Nuc not only accerelated autoimmune disease in lupus-prone MRL/lpr mice but also induced autoimmunity in naive mice. In order to elucidate the role of Nuc in autoimmunity, we first constructed B6 background mice deficient for Nuc gene(nuc) by homologous recombination and mated with MRL/lpr mice to give F, mice and backcrossed the Fj to MRL/lpr mice to obtain nuc-/- in the backgroud of Ipr mice. At the 3rd generation of nuc-/- mice, 4 of 7 mice were found to be suffered from severe lymphadenopathy as compared with wild MRL/lpr mice and the level of anti-dsDNA antibody of IgG class was significantly higher than that of wild MRL/lpr mice. Histopathological findings of the kidney of these mice have shown crescentic and / or sclerotic glomerulonephritis accompanied by necrotizing vasculitis in medium-sized arteries. All mice having such pathological findings produced anti-neutrophil cytoplasmic antibody(ANCA). Production of ANCA indicates that the formation of such a disease slate owes, if not all, to inflammation. Recent studies using yeast two hybrid system indicate that Nuc binds to not only heterotrimeric G protein(G protein) but also cyclooxygenases(Cox). Thus, it is speculated that those inflammation seen in nuc-/- mice is due to dysregulation of G protein as well as prostaglandin-synthesizing Cox in the absence of Nuc.
|出版ステータス||Published - 01-12-1996|
All Science Journal Classification (ASJC) codes
- Molecular Biology