Disease relevance of Gnpda1

• It was reported that a hamster protein, called "oscillin," with a sequence related to that of an Escherichia coli GNPDA triggered Ca(2+) oscillations in mammalian oocytes when introduced into their cytoplasm upon fertilization [1].
• We have therefore compared the effects of various novel dimethanesulfonate compounds (related to BU) in terms of their toxicity to different stem cell subsets in vivo and in vitro and their ability to provide for long-term donor bone marrow engraftment using the congenic glucose-6-phosphate isomerase type 1 marker [2].
• Glucose-6-phosphate isomerase (GPI) is the target autoantigen recognized by KRN T cells in the K/BxN model of rheumatoid arthritis [3].

High impact information on Gnpda1

• To investigate B cell tolerance to GPI in nonautoimmune mice, we increased the GPI-reactive B cell frequency using a low affinity anti-GPI H chain transgene [4].
• Importantly, the LN anti-GPI B cells remained functionally competent and could be induced to secrete autoantibodies in response to cognate T cell help in vitro and in vivo [4].
• B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid [5].
• Pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model [5].
• Analysis of the chimerism by glucose- 6-phosphate isomerase (GPI) assay revealed that alpha5 -/- cells contributed to all the tissues analyzed [6].

Biological context of Gnpda1

• Using specific primers, we performed an RT-PCR analysis to determine the tissue distribution of mouse GNPDA/oscillin mRNA [1].
• Transgenic (Tg) expression of a KRN T cell receptor (TCR) agonist under the major histocompatibility complex class II promoter resulted in thymic deletion with loss of anti-GPI T and B cell responses and attenuated arthritis course [7].
• By using as a marker glucose-6-phosphate isomerase (Glc-6-PIase; glucosephosphate isomerase, D-glucose-6-phosphate ketolisomerase, EC 5.3.1.9), known to map on chromosome 7, this entire chromosome could be excluded as a possible carrier of the Glc-6-Pase structural gene [8].
• The GPI-reactive TCR of standard K/BxN mice induced the transcriptional activation of the IL-4 locus in CD4(+) T cells and eosinophils, and CD4(+) T cells were the obligatory source of IL-4 for disease [9].
• In the present article, we have used isoenzyme variants of glucose-6-phosphate isomerase (GPI) as genetic markers of host and donor genomes in the mouse [10].

Anatomical context of Gnpda1

• Immunofluorescent analysis of the localization of GNPDA in male reproductive tissue revealed its presence in spermatids and in spermatozoa [11].
• These data suggest that GNPDA might play a role in the acrosome reaction [11].
• In the mouse, the nature and role of such a GNPDA/oscillin is not known, but another candidate protein, tr-kit, has been proposed as a sperm factor causing oocyte activation [1].
• Unlike tr-kit mRNA which is expressed solely in mouse testis, GNPDA/oscillin mRNA is detected in unfertilized oocytes and in all tissues examined including testis, heart, thymus, liver, ovary, uterus, kidney, spleen, and lung [1].
• To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patients we have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice [5].

Associations of Gnpda1 with chemical compounds

• Azaserine inhibits FGAM synthetase and glucosamine-6-phosphate isomerase [12].
• The fraction with Ca2+ releasing activity was precipitated by 50% saturating solutions of ammonium sulfate and Western blot analysis showed that the pellets contained glucosamine-6-phosphate deaminase (gpd)/oscillin, a protein which has been suggested to be the sperm's active component [13].
• RESULTS: ELISA revealed positive responses to glucose-6-phosphate isomerase, chondroitin sulfate B, collagen I, collagen II, aggrecan, and DNA between 4 and 12 months post-pristane injection [14].
• CaNAG3, CaNAG4, and CaNAG6 form a gene cluster with CaNAG1 CaNAG2 and CaNAG5 that are responsible for glucosamine-6-phosphate deaminase, N-acetylglucosamine-phosphate deacetylase and N-acetylglucosamine kinase, but their functions largely remain unclear [15].

Other interactions of Gnpda1

• DON inhibits FGAM synthetase, CTP synthetase, and glucosamine-6-phosphate isomerase [12].

Analytical, diagnostic and therapeutic context of Gnpda1

• We report here the molecular cloning and sequencing of mouse GNPDA/oscillin, which shows over 96% identity with the hamster and human homologs [1].
• Indirect immunofluorescence studies, using an antibody raised against hamster GNPDA, demonstrate that GNPDA is lost with the acrosome reaction of mouse spermatozoa, is localized in the equatorial and neck regions of the human spermatozoa and the post-acrosomal region of the hamster spermatozoa [1].
• Recipient C57BL/6J (glucose-6-phosphate isomerase b) mice that received 3-Gy total-body irradiation and 13 Gy to the right hind limb were injected i.v. with GB1/6 cells [16].
• The isoenzymes of glucose-6-phosphate isomerase (GPI) have been used as markers to distinguish the contribution of host and donor tissues to these allografts [17].
• Irradiated host mice were reconstituted with bone marrow cells from a second strain of mice: the two strains were each homozygous for one of the two different isoenzyme forms of the enzyme glucose-6-phosphate isomerase, which enable cells of the two strains to be identified by different isoenzyme mobilities on starch gel electrophoresis [18].

References