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Results for “BALB/c mouse model”

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PubMed2001

Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603.

Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-gamma or tumor necrosis factor-alpha have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4(+) helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.

Acute Disease↗

PubMedDate not supplied

Genetic control of susceptibility to autoimmune gastritis.

A familial component to the tendency to develop autoimmune gastritis has long been recognized. Although linkage to certain HLA alleles and an association with the endocrine autoimmune diseases thyroiditis and type 1 diabetes have been reported, little further progress has been achieved in clinical studies. In contrast, the mouse model of gastritis induced in the BALB/c strain by thymectomy in the third day of life has identified four linkage regions; two on distal chromosome 4 (Gasa1 and Gasa2), one on chromosome 6 (Gasa3) and one in the H2 (Gasa4). Three of these four genes colocalize with NOD mouse diabetes susceptibility genes--the strongest concordance identified to date between any two autoimmune diseases--reflecting the association between autoimmune diabetes and type 1 gastritis in humans.

Animals↗

PubMed2006

[Experimental study of pristane-induced murine lupus model].

OBJECTIVE: To establish a mouse model of systemic lupus erythematosus(SLE) and to discuss the role of environmental factors in the pathogenesis of SLE. METHODS: Thirty 10-week-old female BALB/c mice were divided into the model group and control group. The model mice received a single intraperitoneal injection of 0. 5 mL of pristane, while control mice received a single i.p. injection of 0. 5 mL of 0.9% NS. Autoantibodies and proteinuria were detected before injection and monthly thereafter. 8 months after injection, all mice were bled to death. Kidneys were excised to observe the histopathologic evidence of glomerulonephritis. RESULTS: After pristane injection, antinuclear antibody(ANA) and anti-dsDNA antibody appeared in sera as early as 3 months and 4 months respectively. At 8 months, the incidence rates of ANA and anti-dsDNA antibody were 87.5% and 47.8% respectively. The protein concentration of urine in most mice was > or =1+ (300 mg/L). Light microscopy and immunofluorescence of kidney sections indicated glomerulonephritis. In control group, only one serum was ANA low-titer positive and another was anti-dsDNA antibody low-titer positive. The protein concentration of urine was < or = 1+. The histopathology and immunofluorescence showed no evidence of glomerulonephritis. Spearman correlation analysis indicated that anti-dsDNA antibody was correlated with proteinuria (r = 0.538, P = 0.003). CONCLUSION: The murine lupus model can be successfully established in female BALB/c mouse with a single i. p. injection of 0. 5 mL of pristane and the specific autoantibody anti-dsDNA for SLE has appeared in sera of BALB/c mice.

Animals↗

PubMed2006

Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection.

Human metapneumovirus (hMPV)-infected BALB/c mice were treated with ribavirin (40 mg/kg of body weight twice a day intraperitoneally), corticosterone (0.2 mg/ml in water), or both modalities. Ribavirin significantly decreased both hMPV replication in lungs (by 5 log10) and global pulmonary inflammation on day 5 postinfection, whereas glucocorticoids reduced only alveolar and interstitial inflammation, compared to controls.

Animals↗

PubMed1978

[Preliminary data on the protective effect of interferon coupled with liposomes in the mouse-virus model of murine hepatitis].

In MHV3-infected Balb/c mice the antiviral effect of murine interferon could be significantly enhanced by way of entrapment in cationic liposomes; these multi-lamellar spherules, made of egg lecithin, stearylamine and cholesterol, are supposed to exert a target effect leading to a greater accumulation of interferon in the liver and spleen. The possible use of liposomes as vectors of interferon in different viral pathologies is discussed.

Animals↗

PubMed1998

Mycoplasma pneumoniae pneumonia in a mouse model.

To investigate the pathogenesis of acute Mycoplasma pneumoniae infection, BALB/c mice were anesthetized with metofane, and M. pneumoniae was introduced intranasally on days 0, 1, and 2. Mice were sacrificed on days 0-15. A histopathologic scoring system defined inflammatory changes in the lungs on a scale of 0-26 (least to most severe). Broth cultures were positive for all nasal passage and bronchoalveolar lavage (BAL) specimens. Histopathologic scores ranged from 0 to 21. The mean log10 (cfu/mL) were 4.1-6.4 on days 1-10 and >/=1.7 on days 13-15 for nasal passage and BAL specimens. Serum polymerase chain reaction was negative. ELISA for serum IgM and immunoblots for M. pneumoniae antibody were positive in 21 (62%) of 34 and 33 (97%) of 34 infected animals, respectively, at days 8-15. ELISA for IgG antibody was negative. This mouse pneumonia model can be used to study the immunologic and therapeutic responses to acute M. pneumoniae infection.

Animals↗

PubMed2003

Structure-based design and engineering of a nontoxic recombinant pokeweed antiviral protein with potent anti-human immunodeficiency virus activity.

A molecular model of pokeweed antiviral protein (PAP)-RNA interactions was used to rationally engineer FLP-102((151)AA(152)) and FLP-105((191)AA(192)) as nontoxic PAPs with potent anti-human immunodeficiency virus (anti-HIV) activities. FLP-102 and FLP-105 have been produced in Escherichia coli and tested both in vitro and in vivo. These proteins depurinate HIV type 1 (HIV-1) RNA much better than rRNA and are more potent anti-HIV agents than native PAP or recombinant wild-type PAP. They are substantially less toxic than native PAP in BALB/c mice and exhibit potent in vivo activities against genotypically and phenotypically nucleoside reverse transcriptase inhibitor-resistant HIV-1 in a surrogate human peripheral blood lymphocyte (Hu-PBL) SCID mouse model of human AIDS. Rationally engineered nontoxic recombinant PAPs such as FLP-102 and FLP-105 may provide the basis for effective salvage therapies for patients harboring highly drug-resistant strains of HIV-1. The documented in vitro potencies of FLP-102 and FLP-105, their in vivo antiretroviral activities in the HIV-infected Hu-PBL SCID mouse model, and their favorable toxicity profiles in BALB/c mice warrant the further development of these promising new biotherapeutic agents.

Aniline Compounds↗

PubMed2005

A mouse model of aortic angioplasty for genomic studies of neointimal hyperplasia.

We describe here a mouse model of diffuse aortic remodelling triggered by combined endothelial denudation/vascular distension injury using a novel balloon microcatheter. We validated this model in both outbred (NMRI) and inbred (BALB/c, C57BL/6) mouse strains and found evidence for differential strain susceptibility to neointimal hyperplasia, possibly attributable to genetic factors. Neointimal lesions were approximately 50% smaller in the inbred strains, a finding associated with profound cell loss in the aortic media at the early stages of the response to injury. A further insight from this model suggests an essential role for platelets in the initiation of neointimal hyperplasia, which apparently progresses through monocyte influx from the peripheral circulation. Our findings are consistent with monocyte recruitment driving neointimal growth, a minority expressing the endothelial cell marker FVIII. Overall, the time course and gross histological features of vascular remodelling seen here resemble those seen in other rodent models. However, this new mouse model offers distinct advantages over existing ones in that it involves the actual use of a catheter in a clinical manner, and because it allows the recovery of intact RNA from injured vessels in sufficient quantities for downstream molecular analyses.

Angioplasty↗

PubMed1999

BALB/c mice produce blister-causing antibodies upon immunization with a recombinant human desmoglein 3.

Pemphigus vulgaris (PV) is an Ab-mediated autoimmune blistering disease of mucotaneous surfaces. Over 95% of the patients with PV express DR4 or DRw6, and the disease is characterized by the presence of autoantibodies directed against desmoglein 3 (Dsg 3), a protein expressed on keratinocytes. An appropriate animal model is required to understand immunoregulation and to address the role of immunogenetic components in the production of pathogenic Abs that are characteristic of PV. Therefore, we turned to the development of a mouse model. Four strains of female mice (BALB/c, DBA/1, SJL/J, and HRS/J) were screened for their ability to produce pathogenic anti-Dsg 3 Abs. We demonstrated that only BALB/c mice immunized with a full-length Dsg 3 can produce pathogenic Abs capable of causing acantholysis of human foreskin in culture and blistering in neonatal mice. This observation suggested that either H-2d or the BALB background contains the immunogenetic makeup necessary for the production of pathogenic anti-Dsg 3 Abs. No correlation was noted between a given isotype and the pathogenic potential of autoantibodies from different strains of mice. Similarly, the pattern of reactivity of Abs with a panel of 46 synthetic peptides that span the entire Dsg 3 failed to reveal any association between binding specificity and the pathogenic potential, and suggested that pathogenic Abs might recognize conformational epitopes. Moreover, our studies showed that the epitopes recognized by pathogenic Abs are contained within the extracellular Dsg 3.

Animals↗

PubMed1999

Development of Helicobacter pylori infection model in BALB/c mice with domestic cagA-positive and -negative strains in Taiwan.

We aimed to develop an H. pylori-infected mouse model using clinically stored strains in Taiwan and to test whether development of H. pylori infection in an in vivo animal model is related to the status of the cagA gene. A total of 100 male BALB/c mice, 6-8 weeks old, including 80 in the experimental group and 20 in the control group, were used. Two clinically stored H. pylori isolates, a cagA-positive and a cagA-negative strain, were selected to induce the H. pylori infection in half (N = 40) of the mice in the experimental group. Bacterial isolates of 0.8 x 10(9) CFU/ml were orally inoculated in each mouse of the experimental group for three consecutive days. Ten mice in the control group were sacrificed to confirm the initial absence of H. pylori. Eight weeks after inoculation of the experimental group and no inoculation of the remaining 10 mice of the control group, each mouse was killed. Gastrectomy was then performed for rapid urease test (CLOtest) and histology. In the control group, none of 20 mice had positive results from the CLOtest or histology. In contrast, excluding eight of 80 mice that died before the eighth week, 90.3% (65/72) of the mice challenged with H. pylori showed persistent presence of H. pylori by histology. The severity of gastritis at the eighth week was more evident in H. pylori-infected mice than in control and noninfected mice (P < 0.05). Although gastritis was more severe in mice inoculated with the cagA-positive strain than with the cagA-negative strain, the rates of H. pylori infection in mice were not different between cagA-positive and -negative strains (91.4% vs 89.2%, P > 0.05). In summary, stored strains of H. pylori can be applied to induce an infection model in BALB/c mice. The less virulent cagA-negative strain can induce H. pylori infection in mice as effectively as the cagA-positive strain. The high prevalence of cagA-positive strains in Taiwanese patients may be related to factors other than only the cagA gene of the bacteria.

Animals↗

PubMed2005

Immunization with the Chlamydia trachomatis major outer membrane protein, using adjuvants developed for human vaccines, can induce partial protection in a mouse model against a genital challenge.

To test several vaccines for Chlamydia trachomatis we vaccinated BALB/c and C3H/HeN female mice with a purified preparation of the native mouse pneumonitis (MoPn) major outer membrane protein (MOMP). The MOMP was formulated with anyone of three different adjuvants MF59, LT-K63 or LT-R72. As a negative control the animals were immunized with ovalbumin. Positive controls were inoculated intranasally (i.n.) with 10(4) inclusion-forming units (IFU) of C. trachomatis MoPn. High levels of Chlamydia-specific antibodies were detected in the serum and vaginal washes of the mice immunized with MOMP. Using a lymphoproliferative assay (LPA) a significant response was obtained in splenocytes from most of the groups of mice vaccinated with MOMP. Two weeks after the last immunization the mice were challenged in the left ovarian bursa with 10(5) IFU of C. trachomatis MoPn and vaginal cultures were collected for a period of 6 weeks. Overall, BALB/c and C3H/HeN mice immunized with MOMP showed a decrease in the severity and length of the infection but the difference with the controls was not statistically significant. Following mating the percentage of mice with bilateral fertility was not significantly different between mice vaccinated with MOMP and their respective ovalbumin-immunized controls. However, the C3H/HeN mice immunized with MOMP using MF59 or LTR72 as adjuvants had significantly more embryos per mouse than the control groups. In conclusion, mice immunized with native MOMP and adjuvants developed for human vaccines showed significant Chlamydia-specific immune response and a limited protection against infection and long-term sequelae.

Animals↗

PubMed1993

Genomic organization of the mouse Lmp-2 gene and characteristic structure of its promoter.

Major histocompatibility complex (MHC) class-I molecules present antigenic peptide fragments to cytotoxic T-cells. The peptides are generated in the course of antigen processing from endogenously synthesized cytosolic proteins, and transported into the endoplasmic reticulum to associate with an MHC class-I molecule. So far, at least four genes, Lmp-2, -7, and Tap-1, -2, have been identified between the Pb and Ob genes of the mouse MHC class-II region. The genomic organization of mouse Lmp-2, a gene encoding a subunit of a large intracellular protein complex, was studied. A genomic clone has been isolated that covers the entire mouse Lmp-2 gene. We have determined the nucleotide sequence of the region encompassing the whole Lmp-2 gene and three exons of Tap-1, which spans 8 kb in the mouse genome. The two genes are situated in opposite directions. The transcription start points (tsp) of the two genes, identified by primer extension analysis, are only 118 bp apart. Both promoter regions upstream from the tsp have neither TATA consensus sequences nor other regulatory elements, like an interferon-response element, in spite of their interferon-inducible expression. The Lmp-2 sequence from a non-obese diabetic (NOD) mouse, a model animal for autoimmune diabetes, was compared with that from a Balb/c mouse.

Amino Acid Sequence↗

PubMed2003

Leishmania donovani-derived lipophosphoglycan plus BCG induces a Th1 type immune response but does not protect Syrian golden hamsters (Mesocricetus auratus) and BALB/c mice against Leishmania donovani.

The efficacy of Leishmania donovani-derived lipophosphoglycan (LPG) plus Mycobacterium bovis Bacille Calmette-Guerin (BCG) as a vaccine candidate against visceral leishmaniosis in susceptible BALB/c mouse and Syrian golden hamster (Mesocricetus auratus) models was investigated. Following a triple vaccination with a total dose of 150 microl BCG plus 60 microg or 30 microg of LPG for hamsters and BALB/c mice respectively, there were no noticeable side effects both locally and systemically; implying that the molecule was safe at this dosage level. Vaccinated animals demonstrated an activation of both the humoral as well as cell-mediated responses to LPG, which correlated with resistance against the disease. Protection by LPG plus BCG, was however, poor as the remaining immunized animals showed disease progression leading to severity of the disease as illustrated by emaciation, mass loss and heavy splenic parasitaemia in hamsters. These data nevertheless suggest that it may be rewarding to further evaluate the potential of LPG as a vaccine candidate in leishmaniosis using other adjuvants, which may enhance its immunogenicity.

Adjuvants, Immunologic↗

PubMed1992

Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy.

The incidence of congenital toxoplasmosis was determined by an ELISA in the litters of BALB/c mice which had been infected 8 weeks before mating, on day 12 of pregnancy, or on both these occasions. Of those mice given the infection for the first time on day 12 of pregnancy, 5 out of 6 gave birth to infected litters with approximately 50% of the individuals in each litter being infected. BALB/c mice which had been infected 8 weeks before mating did not give birth to infected litters, even if they were reinfected on day 12 of pregnancy. Following infection BALB/c mice were found to harbour significantly fewer tissue cysts than the congenic H-2 derivative BALB/K strain. However, chronically infected BALB/K mice also failed to produce infected litters, indicating that tissue cyst burden in the dam did not influence congenital infection at least on the BALB background. This study demonstrates that BALB/c dams chronically infected with Toxoplasma gondii, have immunity capable of protecting their embryos from congenital infection, even if the dams are reinfected during pregnancy. Our results demonstrate that the BALB/c mouse can be used as a model of human or ovine congenital T. gondii infection suitable for testing putative vaccines.

Animals↗

PubMed1994

Comparison of corticosteroid- and L3T4+ antibody-immunosuppressed mouse models of Pneumocystis carinii pneumonia for evaluation of drugs and leukocytes.

An immunologically immunosuppressed mouse model of Pneumocystis carinii pneumonia using antibody developed by Dialynas et al. (Immunol. Rev. 74:29-55, 1983) directed to L3T4+ T cells (referred to as L3T4+ antibody) was compared with a corticosteroid-immunosuppressed mouse model. Corticosteroid- or L3T4+ antibody-immunosuppressed BALB/c mice transtracheally inoculated with P. carinii developed severe infections within 5 weeks after inoculation and responded to treatments with an echinocandin B analog, LY302146, or trimethoprim plus sulfamethoxazole so that they had decreased numbers of P. carinii cysts and trophozoites. LY302146 appeared to be more effective in L3T4+ antibody-immunosuppressed mice than in dexamethasone-immunosuppressed mice. Leukocyte populations in lungs of both mouse models during development of infection and during treatment were compared by using immune cell-specific staining. Lungs of L3T4+ antibody-immunosuppressed mice had many more cells detected with pan-B antibody and pan-T antibody than dexamethasone-immunosuppressed mice and the lungs of successfully treated mice had about the same numbers of macrophages as those of nonimmunosuppressed uninfected mice. The immunologically immunosuppressed model will allow study of cytokines and other immune modulators alone and in combination with drugs.

Animals↗

PubMed1999

Acute murine cytomegalovirus infection: a model for determining antiviral activity against CMV induced hepatitis.

Acute intraperitoneal infection of weanling BALB/c mice with murine cytomegalovirus (MCMV) resulted in an inoculum titer-dependent weight loss, mortality and elevation of plasma transaminases (ALT: alanine transaminase and AST: aspartate transaminase). Three days post infection (p.i.) with 10(4.85) plaque forming units (pfu) there was 90% mortality with a mean death day p.i. of 4.1 +/- 0.2. Plasma levels of ALT and AST were elevated 24- and 15-fold, respectively. Organ titers of virus (log10 pfu/g tissue) were 6.16 in the liver, 6.05 in the spleen, 4.0-4.7 in the lung, heart, kidney and intestine and undetectable in the muscle and brain. Organ concentrations (units/g wet-weight) of ALT were highest in the liver, whilst for AST the highest levels were found in the heart. The concentrations of ALT but not AST were reduced (35-55%) in the infected liver; the concentrations of ALT and AST were not changed in other infected organs. There were excellent correlations (r > 0.95) between viral titers in the liver, increases of plasma ALT and depletion of liver ALT. HPMPC and ganciclovir administered either p.o. or s.c. reduced mortality, increases in plasma transaminases and viral burdens in the liver and prevented depletion of liver ALT. HPMPC was approximately 10-fold more potent than ganciclovir. These results strongly suggest that intraperitoneal infection of the BALB/c mouse with MCMV represents an animal model of CMV hepatitis that can be monitored by measuring plasma ALT.

Alanine Transaminase↗

PubMed2006

Spontaneous murine neuroaxonal dystrophy: a model of infantile neuroaxonal dystrophy.

The neuroaxonal dystrophies (NADs) in human beings are fatal, inherited, neurodegenerative diseases with distinctive pathological features. This report describes a new mouse model of NAD that was identified as a spontaneous mutation in a BALB/c congenic mouse strain. The affected animals developed clinical signs of a sensory axonopathy consisting of hindlimb spasticity and ataxia as early as 3 weeks of age, with progression to paraparesis and severe morbidity by 6 months of age. Hallmark histological lesions consisted of spheroids (swollen axons), in the grey and white matter of the midbrain, brain stem, and all levels of the spinal cord. Ultrastructural analysis of the spheroids revealed accumulations of layered stacks of membranes and tubulovesicular elements, strongly resembling the ultrastructural changes seen in the axons of human patients with endogenous forms of NAD. Mouse NAD would therefore seem a potentially valuable model of human NADs.

Animals↗

PubMed2001

Detection of Mycobacterium tuberculosis group organisms in human and mouse joint tissue by reverse transcriptase PCR: prevalence in diseased synovial tissue suggests lack of specific association with rheumatoid arthritis.

Infection with mycobacterial species, including Mycobacterium tuberculosis, has long been implicated in the etiopathology of rheumatoid arthritis (RA) on the basis of clinical and pathological similarities between tuberculosis and RA. Despite evidence of immune responses to mycobacterial antigens in RA patient synovial fluid, cross-reactivity between these and host joint antigens, and the presence of M. tuberculosis protein antigen in RA synovial fluid, a definite causal association with RA has not been shown. Previous studies from our laboratory using reverse transcriptase PCR (RT-PCR) of bacterial rRNAs have shown RA synovium to be colonized by a diverse range of bacteria, most of commensal origin. However, M. tuberculosis group organism (MTG) RNA sequences were found in one RA patient tissue. Since this was considered of sufficient interest to warrant further investigation, we devised a M. tuberculosis-specific nested RT-PCR test which could be used for detection of MTG in a mixed pool of bacterial crDNAs. This test was used to investigate the distribution of MTG in RA synovial tissue and also non-RA arthritis and healthy control tissues and was also used to examine the tissue distribution of MTG in an acute and chronic model of M. tuberculosis infection in the BALB/c mouse. MTG sequences were found in a high proportion of RA patient synovial tissues but also in non-RA arthritis control tissues at lower frequency. This likely reflects trafficking of persistent M. bovis BCG to inflamed joint tissue, irrespective of cause. MTG were not found in healthy synovial tissue or the tissue of patients with undifferentiated arthritis. In both the acute and chronic models of infection in BALB/c mice, M. tuberculosis was also found to have trafficked to joint tissues, however, no signs of inflammation, arthritis, or pathology associated with M. tuberculosis infection was seen. These combined results would argue against a specific causal role of MTG in RA-like arthritis; however, their role as adjuvant in immune dysfunction in an innately susceptible host cannot be excluded.

Acute Disease↗