Platelet-activating factor (PAF) has been suggested recently to play an important role in immune glomerulonephritis, favoring the formation of immune deposits in glomeruli and contributing to the local inflammatory reaction. Here we sought to investigate whether urinary PAF excretion was modified in New Zealand Black x New Zealand White mice a model of genetically determined immune complex disease which mimics systemic lupus in humans and whether changes in PAF urinary excretion values correlated with the extent of proteinuria. To clarify the possible in vivo relevance of these findings we evaluated whether PAF receptor antagonist has any influence on the evolution of renal disease and survival of these mice. Our results showed that: 1) in lupus mice urinary PAF excretion increased progressively with age in New Zealand Black x White; 2) the increase in PAF excretion correlated with the severity of proteinuria; and 3) the chronic administration of a PAF receptor antagonist [L-659,989 [(+/- ...
TY - JOUR. T1 - Neurotropin improves the apoptotic thymic defects of New Zealand Black mice. AU - Takeoka, Y.. AU - Taguchi, N.. AU - Naiki, M.. AU - Ansari, A. A.. AU - Gershwin, M. Eric. PY - 1999. Y1 - 1999. N2 - New Zealand Black (NZB) mice serve as a model of human systemic lupus erythematosus. Both humans and mice with systemic lupus erythematosus share many clinical and pathologic abnormalities. These includes the finding that both have histologic abnormalities of the thymic microenvironment, including an irregular shape of medullary epithelial clusters and a diffuse corticoepithelial network. It is believed that these abnormalities of the thymic microarchitecture contribute to abnormalities associated with positive and negative selection, the latter being molecules by apoptosis. Previous work has demonstrated that the administration of neurotropin, a unique nonprotein extract, isolated from the inflamed dermis of rabbits inoculated with vaccinia virus, has beneficial effects in murine ...
Male F1 New Zealand Black X New Zealand White mice, which spontaneously develop immune complex renal disease, underwent unilateral nephrectomy at 3 months of age and were compared with sham-operated controls. At 12 months of age only 24% of mice with a single kidney were alive, while 85% of sham-operated controls survived to the same age. Unilaterally nephrectomized mice had more severe renal histologic changes, as shown by light and immunofluorescence microscopy. ...
Moutsopoulos, H M. and Chused, T M., Demonstration of activation of b lymphocytes in new zealand black mice at birth by an immunoradiometric assay for murine igm. (1977). Subject Strain Bibliography 1977. 45 ...
We designed a polyethylene glycol precipitation method for detecting retroviral gp70-anti-gp70 immune complexes (gp70 IC) in the circulation of mice. To determine the genetic contribution of NZB and NZW strains to the spontaneous occurrence of circulating gp70 IC in NZB X NZW (B/W)F1 hybrids, we measured these IC in female NZB, NZW, (NZB X NZW)F1 (B/W F1), B/W F1 X NZW backcross, and B/W F1 X NZB backcross mice. The highest amounts of gp70 IC were found in B/W F1 and the lowest in NZW mice, and the order of the average serum levels was B/W F1, B/W F1 X NZB, B/W F1 X NZW, NZB, and NZW. Genetic analyses suggested that two major dominant genes, one from NZB and the other from NZW, are involved in the formation of these gp70 IC. A single dominant gene of NZB strain determines the formation of these IC, and the magnitude is to a great degree modified (intensified) by the NZW gene. In addition, statistical analyses of data obtained in the studies of B/W F1 X NZW backcrosses suggested the presence of ...
Gershwin, M E.; Castles, J J.; Saito, W; and Ahmed, A, Studies of congenitally immunologically mutant new zealand mice. Vii. The ontogeny of thymic abnormalities and reconstitution of nude nzb/w mice. (1982). Subject Strain Bibliography 1982. 3624 ...
TY - JOUR. T1 - Expansion of bone marrow IFN-α-producing dendritic cells in New Zealand Black (NZB) mice. T2 - High level expression of TLR9 and secretion of IFN-α in NZB bone marrow. AU - Lian, Zhe Xiong. AU - Kikuchi, Kentaro. AU - Yang, Guo Xiang. AU - Ansari, Aftab A.. AU - Ikehara, Susumu. AU - Gershwin, M. Eric. PY - 2004/10/15. Y1 - 2004/10/15. N2 - Patients with systemic lupus erythematosus have elevated IFN-α production. Furthermore, sera IFN-α levels correlate with disease activity. We have focused our attention on whether this phenotype is also seen in the New Zealand Black (NZB) mice and simultaneously addressed the underlying mechanisms. Specifically, we analyzed: 1) levels of sera IFN-α after type A CpG ODN 2216 injection in autoimmunity-prone NZB and control mice, and 2) levels of IFN-α synthesized by IFN-α-producing dendritic cells (IPDCs) using highly enriched populations of CD11c+B220+ IPDCs derived from NZB and control mice; IPDCs are divided into two subpopulations ...
TY - JOUR. T1 - An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice. AU - Nelson, R. K.. AU - Gould, K. A.. PY - 2016/2/1. Y1 - 2016/2/1. N2 - Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell-specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB × NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4+ and CD8+ T cells, the proportion of ...
0003] Recent studies have demonstrated that IL-18 levels are associated with the severity of renal damage in patients with SLE and in lupus-prone New Zealand black/white (NZB/W) F1 mice (Shui, H. A. et al. LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis. Rheumatology (Oxford) 46:1277-1284; 2007) or MLR/lpr mice (Faust, J. et al. Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus nephritis. Arthritis Rheum 46:3083-3095; 2002). NOD-like receptor (NLR) family members are a group of pattern recognition receptors involved in a wide variety of microbial components and danger signals. In response to pathogen-associated molecular patterns or danger signals, a subset of NLRs forms a complex with apoptosis-associated speck-like protein that contains a caspase recruitment domain to activate caspase-1 (Franchi, L. et al. The inflammasome: a caspase-1-activation platform ...
TY - JOUR. T1 - T cell abnormalities in NZB mice occur independently of autoantibody production. AU - Taurog, J. D.. AU - Raveche, E. S.. AU - Smathers, P. A.. AU - Glimcher, L. H.. AU - Huston, D. P.. AU - Hansen, C. T.. AU - Steinberg, A. D.. PY - 1981/5/15. Y1 - 1981/5/15. N2 - By means of a series of crosses and backcrosses, ZB.CBA/N mice were prepared bearing largely NZB autosomal genes, but having X chromosomes derived only from CBA/N mice. The CBA/N X chromosome carries a gene, xid, that is associated with the lack of a B cell subset necessary for most of the spontaneous autoantibody production by NZB mice. These ZB.CBA/N mice failed to develop autoantibodies to T cells, erythrocytes, or DNA. The availability of mice that were mostly NZB, but which failed to make autoantibodies, especially anti-T cell antibodies, allowed us to study possible T cell regulatory defects in NZB mice in the absence of either antibodies reactive with such T cells or other autoantibodies. We found that such mice ...
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Systemic lupus erythematosus is an autoantibody mediated disease that causes immune complex glomerulonephritis as well as injury to multiple organs. Invariant natural killer T cells (iNKT) from non-autoimmune strains of mice regulate and suppress graft versus host disease, transplantation immunity and autoimmunity. We have shown that iNKT cells from lupus prone NZB/W mice are abnormal and promote rather than suppress spontaneous in vitro immunoglobulin and autoantibody secretion of autoreactive B cells. To determine the role of iNKT cells in the induction and augmentation of immune cell activation, we examined cytokine production of purified iNKT cells from NZB/W and control C57BL/6 mice in vitro. We found that upon stimulation of NKT stimulatory ligand, α-galactosylceramide, young NZB/W splenocytes secreted much higher IFNγ, IL-4 and IL-17 compared with C57BL/6 mice. With activation of CD3 and CD28, sorted NZB/W splenic iNKT cells, but not conventional T cells, also produced dramatically ...
Systemic lupus erythematosus (SLE) is a severe systemic chronic autoimmune disease and NZB/W F1 mice are commonly used to study this disease. The role of interleukin 10 (IL10) in SLE is controversial and needs to be clarified, especially with regard to the different cell types which can produce IL10. Here the authors show that IL10 produced by CD4 T cells plays a beneficial role in murine lupus of NZB/W F1 mice, even in full-blown disease in old NZB/W F1 mice. The authors (1) detected SmD1(83-119)-specific CD4 IL10 T cells after a previously published SmD1(83-119) high-dose tolerisation protocol1 and were able to increase the number of these cells by an additional booster immunisation with SmD1(83-119); (2) showed that IL10 has a suppressive effect on anti-dsDNA autoantibody production at least in vitro; (3) achieved a temporary beneficial effect on the course of proteinuria and autoantibody development by transfer of CD4 T cells containing up to 0.04% SmD1(83-119)-specific CD4 IL10 T cells from ...
TY - JOUR. T1 - Effect of late modulation of nitric oxide production on murine lupus. AU - Oates, James C.. AU - Ruiz, Philip. AU - Alexander, Audrey. AU - Pippen, Anne M.M.. AU - Gilkeson, Gary S.. PY - 1997/4. Y1 - 1997/4. N2 - MRL/MpJ-Fas(lpr) (MRL-lpr) and New Zealand Black/White (NZB/W) mice develop spontaneous autoimmune disease characterized by autoantibody production and glomerulonephritis that progresses in parallel with increasing systemic nitric oxide (NO) production. A previously published study from our laboratory indicated that oral administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (NMMA) before the onset of clinical disease significantly decreased renal and joint pathology in MRL-lpr mice. To characterize the effect of late modulation of NO production in murine SLE, we administered oral NMMA and/or restricted dietary arginine after disease onset in two murine models of SLE. When receiving combined NMMA and arginine restriction, MRL-lpr mice had ...
In mice, genome-wide linkage studies have implicated the syntenic region to human 1q23 in three different models of spontaneous lupus: the (NZB × NZW)F2 intercross, the NZM/Aeg2410 New Zealand mice, and the BXSB mice (Kono et al., 1994; Rozzo et al., 1996; Hogarth et al., 1998). The phenotype of these mice is very similar to that in SLE patients, with the production of autoantibodies, as well as multiorgan involvement, including severe nephritis. In congenic mice derived from the NZM2410 mouse strain and B6, the locus on chromosome 1, i.e., Sle1, by itself was sufficient to generate a strong, spontaneous, humoral ANA response. Sle1 also led to an expanded pool of histone-reactive T cells. Thus, Sle1 may lead to the presentation of chromatin in an immunogenic fashion or directly impact tolerance of chromatin-specific B cells. Consequently, Sle1 is thought to be a major player in orchestrating selective loss of B cell and T cell tolerance to chromatin. Fine mapping of the Sle1 locus determined ...
Hereditary lupus of NZB/W mice is an Ab-mediated systemic autoimmune disease in which the Th1 cytokine IFN-γ has been shown to play an important role in the pathogenesis of tissue injury (57). Anti-IFN-γ mAb treatment has been reported to ameliorate the immune complex glomerulonephritis, the hallmark of the disease (21). In addition, introduction of a transgene encoding the Th2 cytokine IL-4 into lupus-prone (NZW × C57BL/6.Yaa) F1 mice prevented lupus development (58). We have recently reported that adoptive transfer of CD1d-reactive transgenic CD4 T cells with a Th1-like cytokine-secretion pattern induced lupus in BALB/c nu/nu recipients (8). CD1d-reactive T cells have also been suggested to play a role in augmenting IgG2a anti-dsDNA secretion and lupus development in lupus-prone NZB/W mice (20). It is not yet clear, however, whether activation of the CD1d-reactive T cells in NZB/W mice contributed to the IFN-γ secretion that shifted the autoantibody secretion toward the pathogenic IgG2a ...
Fingerprint Dive into the research topics of Altered bax expression and decreased apoptosis in bone marrow cells of lupus-susceptible NZB/W mice. Together they form a unique fingerprint. ...
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Results In untreated mice uNGAL resulted 38.7±26.7 ng/ml at 18 weeks and it increased from 24 weeks of age (120±3.5 ng/ml) reaching a pick after 35 weeks of age (180.5±42.5 ng/mg). At 24 weeks uNGAL was 32.7±24.6 ng/ml in NZB/W20, 30.4±17 ng/ml in NZB/WM24. At 35 weeks of age uNGAL was 184.6±28.2 ng/ml in NZB/W20, 84.4±27.8 ng/ml in NZB/W24 and 158±66.2 ng/ml in NZB/W32. At 35 weeks of age uNGAL was 152.5±99.5 in NZB/WM20 and 49.5±8 ng/ml in NZB/WM24 (p=0.009 if compared to untreated mice). No differences in uMCP-1 were detected into the different treatment arms if compared to the controls. ...
Chimpanzees, which are struggling to survive as a species, may have gotten a new lease on life last week, thanks to some lowly white laboratory mice in California.Bitter arguments about the future
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Affiliation:兵庫医科大学,医学部,教授, Research Field:内科学一般,Orthopaedic surgery,Immunology,Psychiatric science,Collagenous pathology/Allergology, Keywords:IL-18,IL-6,TLR4,IL-12,NZB/WF1,多発性骨髄腫,interleukin-18,CD3^|int|Il-2Rbeta^+T cells,FasL dependent,cancer, # of Research Projects:7, # of Research Products:13, Ongoing Project:羊膜間葉系幹細胞によるステロイド抵抗性膠原病・膠原病類縁疾患に対する治療の確立
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1. A 21-day whole body x-irradiation LD50 was determined for guinea pigs, white mice and deer mice. As measured by post-exposure deaths, guinea pigs were most susceptible (LD50: 163 r), white mice less susceptible (LD50: 431 r) and deer mice least susceptible (LD50: 588 r) to the irradiation. 2. In a pilot rickettsiae study, Coxiella burnetii was shown to persist for over 12 weeks in kidneys of guinea pigs and reproductive tract and kidneys of white mice. Fecal material and urine in guinea pigs, white mice and deer mice were infectious for three weeks. The organism persisted a total of six week in deer mouse spleen, kidneys and liver. 3. Whole body x-irradiation in dosages slightly less than or greater than the 21-day LD50 caused a reactivation of C. burnetii infection in guinea pigs, white mice, and deer mice infected three months previously. This reactivation was determined by demonstrating infectious quantities of rickettsiae in various tissues and in urine and feces in these animals, as ...
In the analysis of genes contributing to disease in animal models of autoimmunity, the affected strain is usually outcrossed to another strain that does not express the phenotype being studied. Whether the genes from the unaffected or non-autoimmune strain can change the results of linkage analyses has not been directly studied. McAleer et al. (23) analyzed genes contributing to insulin-dependent diabetes in NOD mice in outcrosses to MHC-congenic NON mice and compared results to previous outcrosses with C57BL/10 mice. Background genetic influences from NON versus C57BL/10 strains were apparent, but the fact that NOD and NON are related backgrounds likely influenced some of the findings. Furthermore, the comparison was retrospective, which could have introduced another variable. In our study, we used two well-studied and unrelated normal strains, C57BL/6J and BALB/cJ, and all backcross progeny were bred and followed for disease concomitantly. Our results indicate that the genetic background of ...
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The rate of respiration and ATP synthesis in liver mitochondria of newborn BL/6NZB mice was slightly lower than BL/6C57 mice. Subsequently, these variables equalized, then from 100-day-old onwards the rates in BL/6C57 mice decreased gradually, while in BL/6NZB they remained constant.. Interestingly, in young BL/6NZB mice (126 days) the liver and heart tissues had elevated mitochondrial ROS level measured by the mitochondrial probe MitoB [15] (Fig. 2c). On the contrary, in adult BL/6NZB animals (210 days) mitochondrial H2O2 level was lower than that of BL/6C57 (Fig. 2d). It is suggested that an adaptive response (hormesis) may take place, wherein an elevated level of ROS at the young age prevents its subsequent increase and thus prolongs lifespan. It should be noted that the method of mitochondrial H2O2 measurement using MitoB probe has been tested in just a few laboratories, so it is difficult to define its suitability. In addition to a number of high-tech procedures, oxidative damage of ...
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Previously, it was shown that TLR7-MyD88-dependent RNA sensing is absolutely crucial for the formation of Spt-GCs and the development of autoimmunity (2, 9-11). This led us to ask whether cytosolic RNA sensing by RLRs may also be equally crucial for the formation of Spt-GC responses. We also approached this study with the intention of gaining more information about how the analysis of these responses should be approached in autoimmune-prone mouse strains. Whereas endosomal TLR7-MyD88 signaling promotes Spt-GC responses in both healthy and autoimmune-prone mice on a B6 background (10), we found that cytosolic MDA5-MAVS signaling did not have a significant role in the magnitude of GC formation on a similar B6 background. More intriguingly, we found MAVS phenotypes to be dependent on the genetic background as MAVS deficiency on a B6/129 background conversely resulted in nearly absent Spt-GC responses, reminiscent of the Spt-GC responses observed in TLR7KO mice. The lack of Spt-GC response in ...
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