Disease relevance of Mice, Inbred MRL lpr

• Here we report that treatment with an agonistic monoclonal antibody to CD137 (2A) blocks lymphadenopathy and spontaneous autoimmune diseases in Fas-deficient MRL/lpr mice, ultimately leading to their prolonged survival [1].
• Recovery from autoimmunity of MRL/lpr mice after infection with an interleukin-2/vaccinia recombinant virus [2].
• Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment [3].
• MRL/MP-lpr/lpr (MRL/lpr) mice develop a spontaneous autoimmune disease [4].
• Daily injection of recombinant IL-12 led to increased serum levels of IFN-gamma and NO metabolites, and accelerated glomerulonephritis in the young MRL/lpr mice (but not in the MRL/+ mice) compared with controls injected with phosphate-buffered saline alone [4].

High impact information on Mice, Inbred MRL lpr

• MRL/lpr mice are particularly severely affected, and they develop a syndrome that is serologically and pathologically similar to human systemic lupus erythematosus (SLE) [5].
• Here we examine the use of inhibitors of phosphoinositide 3-kinase (PI3K) gamma, a lipid kinase that regulates inflammation, in the MRL-lpr mouse model of SLE [6].
• An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model [7].
• Spleen and peritoneal cells from MRL/lpr mice also produced significantly more nitric oxide (NO) than those from the control mice when cultured with interferon (IFN) gamma and lipopolysaccharide (LPS) in vitro [4].
• It is striking that cells from MRL/lpr mice produced high concentrations of NO when cultured cells from MRL/+ or BALB/c mice [4].

Chemical compound and disease context of Mice, Inbred MRL lpr

• Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice [8].
• Amelioration of autoimmune nephritis by imatinib in MRL/lpr mice [9].
• Caloric restriction of MRL/lpr mice was associated with an increased plaque-forming cell response to trinitrophenylated polyacrylamide beads, less lymphoproliferation, and less severe glomerulonephritis [10].
• Chronic cyclosporine therapy, started at an early age, is effective in controlling the autoimmune disease in MRL/lpr mice, including the ocular and lacrimal gland lesions [11].
• PURPOSE: To determine whether lacrimal and salivary gland nerves of an animal model of Sjögren's syndrome, the MRL/lpr mouse, are able to release acetylcholine [12].

Biological context of Mice, Inbred MRL lpr

• Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice [13].
• Esterolytic antibodies were not found in MRL/lpr mice immunized with haptens that do not mimic the transition state for the hydrolysis of the ester substrate (e.g., with a substrate analog) [14].
• In contrast, the absence of lymproliferation in engineered mutants of 'death pathways' suggests that additional events are necessary to recapitulate the overt phenotype of ALPS patients or MRL/lpr mice [15].
• Mature CD4+ T lymphocytes from MRL/lpr mice are resistant to receptor-mediated tolerance and apoptosis [16].
• Although tolerance to Sm is maintained in 2-12H/bcl-2-22-Tg mice, it is lost in 2-12H-Tg MRL/lpr mice, as the transgene accelerates and increases the prevalence of the anti-Sm response [17].

Anatomical context of Mice, Inbred MRL lpr

• Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice [18].
• The lacrimal gland inflammatory lesions and renal vasculitic lesions of autoimmune MRL/lpr mice were analyzed for the lymphocyte subsets present [19].
• Spontaneous production of tumor necrosis factor alpha by Kupffer cells of MRL/lpr mice [20].
• In aged MRL/lpr mice, although gp130 expression was detectable in splenic CD4(+) or CD8(+) T cells, gp130 expression was significantly downregulated [21].
• A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented [22].

Associations of Mice, Inbred MRL lpr with chemical compounds

• Moreover, these alterations in host defense, including survival in response to lethal infection, could be ameliorated in MRL/lpr mice by the parenteral administration of a monoclonal antibody that neutralizes the activity of TGF-beta [23].
• RESULTS: Diffuse proliferative GN, with deposition of IgG and C3, developed in both FcRgamma(-/-) and FcRgamma(+) MRL/lpr mice [24].
• Second, cyclosporin A, which ameliorates GN in MRL/lpr mice despite autoantibody production, was found to reduce serum IgG3 and mRNA levels, associated with the revision of cationic shift of the serum IgG3 spectrotype seen in isoelectric focusing [25].
• Because dexamethasone (Dex) alters Ia antigen expression and suppresses cytokine generation, the authors prophylactically treated MRL-lpr mice and investigated the relative importance of these molecules in inducing renal injury [26].
• MRL/lpr mice fed a low-fat, calorically restricted diet from 5 months of age to death lived longer than mice which were fed ad libitum a cholesterol-containing, high-fat diet [10].

Gene context of Mice, Inbred MRL lpr

• Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice [27].
• RESULTS: MCP-1 antagonist- or TARC antagonist-transfected MRL/N-1 cells were injected subcutaneously into MRL/lpr mice ages 7 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease) [28].
• beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice [29].
• CONCLUSION: We established a new system using MRL/N-1 cells that allows long-term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice [28].
• MRL/lpr mice demonstrated increased expression of monocyte chemoattractant protein-1, regulated upon activation, normal T cell-expressed and -secreted protein, inducible protein of 10 kD, and macrophage inflammatory protein-1beta at week 8 [30].

Analytical, diagnostic and therapeutic context of Mice, Inbred MRL lpr

• Administration of this peptide to MRL/lpr mice, an animal model used to study SLE, resulted in a remarkable enhancement of the survival rate (80%) compared to placebo-treated animals (10%) [31].
• Epitope mapping with 12 human SLE and 12 MRL/lpr mouse anti-SmB/B' sera revealed that antibodies directed against the X-B peptide accounted for most (65.5 +/- 15.4 and 63.2 +/- 25.3%), B-R intermediate levels (51.5 +/- 30.8 and 18 +/- 19.6%), and F-X none of the anti-SmB activity in human and mouse sera, respectively [32].
• The amount of IL-1beta protein in lacrimal gland acinar cell lysates prepared from 3-, 9-, and 13-week-old BALB/c, MRL/(+), and MRL/lpr mice was determined by ELISA [33].
• We bred MRL/lpr mice with mice lacking CD4+ or CD8+ T cells by gene targeting via homologous recombination in embryonal stem cells to determine the roles of these cells in the autoimmune disease [34].
• The kidneys of MRL-lpr mice were examined before (< 12 weeks of age) and after (> 12 weeks of age) renal injury for CSF-1 transcripts by in situ hybridization [35].

References