Neuronal or inducible nitric oxide synthase (NOS) expression level is not involved in the different susceptibility to nigro-striatal dopaminergic neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) between C57BL/6 and BALB/c mice

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces severe degeneration of dopaminergic (DA-ergic) neurons when administrated to C57BL/6 mice, but such lesions are not observed in BALB/c mice. To clarify the factors which influence such marked strain differences in the susceptibility to MPTP, the involvement of neuronal NOS (nNOS) and inducible NOS (iNOS) was investigated. MPTP was intraperitoneally (ip) administrated to adult C57BL/6 (highly sensitive) and BALB/c (resistant) mice. Immunohistochemical analysis using an antibody to tyrosine hydroxylase (TH) showed a significant decrease in TH-immunopositive areas in the striatum and TH-positive cells in the substantia nigra pars compacta (SNpc) of MPTP-treated C57BL/6 mice at 1 and 7 days (d) after administration, compared to control C57BL/6 mice. On the other hand, MPTP-treated BALB/c mice showed no significant changes. By Western blot analysis, TH, MAO-B, DAT, nNOS and iNOS protein expression levels were examined in intact and MPTP-treated mice. Intact BALB/c mice showed higher DAT protein expression in the striatum and TH protein expression in the midbrain than intact C57BL/6 mice. In addition, MPTP-treated BALB/c mice showed a more significant increase of MAO-B expression than MPTP-treated C57BL/6 mice at 12 h. The increase of nNOS and iNOS protein expressions in MPTP-treated BALB/c mice was more pronounced in the striatum and midbrain than in MPTP-treated C57BL/6 mice at 12 h and 2 d. These results indicate that MAO-B, DAT, nNOS or iNOS expression levels do not influence the different strain susceptibility to MPTP.     

Task-dependent strain difference of spatial learning in C57BL/6N and BALB/c mice

In the present study, we used a dry maze task to assess the spatial learning ability of C57BL/6N and BALB/cA mice besides the water maze task. In Experiment 1, the performance of C57BL/6N and BALB/cA mice in the water maze task and dry maze task were investigated. In the former task, the mice had to learn the position of a hidden platform submerged below the water surface and they had to learn the position of a baited hole on the circular maze in the latter task. C57BL/6N mice showed significant learning in both maze tasks, whereas BALB/cA mice showed learning in a dry maze but not in water maze as reported before. In Experiment 2, a dry maze task was conducted on a circular open field which contained 16 holes arranged symmetrically and which was put on the same height as the surface of the water maze. In Experiment 2, BALB/cA mice showed significant improvement in latency and path length to reach the food hole. The poor performance of the BALB/cA in the water maze task may reflect a weak motivation, escaping from water, rather than the poor spatial memory in this strain.     

Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice

Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations in Th1 cytokines/chemokines, increased numbers of lymphocytes and macrophages in lung lavage fluid, and peribronchovascular granulomatous inflammation composed of T- and B-lymphocytes and epithelioid histiocytes. T-lymphocytes in the lung lavage fluid showed a marked CD4+ cell predominance. In contrast, C57BL/6 mice challenged with Staphylococcus epidermidis (SE), another gram-positive commensal of human skin, and BALB/c mice challenged with PA, showed only a modest induction of Th1 cytokines, less pulmonary inflammation, and no granulomatous changes in the lung. Enhancement of Toll-like receptor expression was seen in PA-exposed C57BL/6 mice within 24 h after exposure, suggesting that induction of innate immunity by PA contributes to the robust, polarized Th1 immune response elicited by this bacterium. These findings suggest that PA-induced pulmonary inflammation may be a useful model for testing the contributions of both bacterial and host factors in the development, maintenance, and resolution of granulomatous inflammation in the lung.     

Multidimensional assessment of differences in monoamine metabolism in C57Bl/6 and BALB/c mice

Monoamine metabolism in the hypothalamus and striatum of BALB/c and C57Bl/6 mice (intact and stressed in the open field test) was studied using single-and multidimensional statistical methods. It is suggested that the revealed difference in neurotransmitter metabolism is associated with genetically controlled behavior of these animals under conditions of emotional stress. The results of discriminant analysis suggest that the regulation of monoamine metabolism during emotional stress is genetically determined. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 574–577, May, 2000     

Contrasting phenotypes of liver-infiltrating leucocytes isolated from MCMV-infected BALB/c and C57 BL/6 mice

We characterized liver-infiltrating leucocytes (LIL) from BALB/c and C57BL/6 mice 0-56 days after murine cytomegalovirus (MCMV) infection. Inflammation clears from C57BL/6 mice 4-5 weeks post infection (pi), but persists for several months in BALB/c mice. The LIL obtained were 60-80% Thy 1.2+ by flow cytometry. The percentage of CD8+ cells rose sharply in all mice 7 days pi, with little decrease in BALB/c mice by day 56. CD4-CD8-Thy 1.2+/TCR alpha beta + cells were more prevalent in LIL than lymph node cells (LNC) irrespective of MCMV infection, whilst infection increased the proportion of CD8+ L-selectin- LIL (but not LNC). LIL from both mouse strains demonstrated cytotoxic activity against YAC-1 cells, but only LIL from BALB/c mice proliferated spontaneously ex vivo 21 days pi, as measured by tritiated thymidine incorporation. BALB/c LIL produced IFN gamma and IgG2a 7-21 days pi, whilst IL-10 secretion was similar in both strains. Thus, persistent hepatitis in BALB/c mice is associated with activation and proliferation of intrahepatic leucocytes with some bias towards a Th1 response.     

Bronchial lesions of the late asthmatic response in BALB/c and C57BL/6 mice

In this study, histopathological bronchial-bronchiolar lesions of the late asthmatic responses induced by ovalbumin in BALB/c and C57BL/6 mice were compared. Prominent goblet cell hyperplasia and metaplasia with mucous secretion, and desquamation of epithelial cells with severe infiltration of eosinophils and lymphocytes, were observed in the BALB/c mice; in the C57BL/6 mice, however, these changes were less severe. The reduced histopathological changes in the C57BL/6 mice were associated with a decreased infiltrate of eosinophils, decreased serum immunoglobulin-E (IgE) concentrations and increased serum interferon-gamma concentrations. The results suggest that the reduced bronchial lesions in C57BL/6 mice were due, at least in part, to suppression of the T-helper (Th)2 immune response that underlies the decreased infiltration of lymphocytes and eosinophils into the bronchial mucosa.     

Antibody and cytokine responses to the cilium-associated respiratory bacillus in BALB/c and C57BL/6 mice

The cilium-associated respiratory (CAR) bacillus is a gram-negative, gliding bacterium that causes persistent respiratory tract infections in rodents despite histologic and serologic evidence of a marked immune response. To assess humoral immunity and cytokine responses in CAR bacillus disease, 6-week-old female BALB/c and C57BL/6 mice were inoculated intratracheally with 10(5) CAR bacillus organisms. CAR bacillus-specific serum immunoglobulins (immunoglobulin M [IgM], IgG1, IgG2a, IgG2b, IgG3, and IgA) and local pulmonary cytokines (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], and interleukin-4 [IL-4]) were evaluated by enzyme-linked immunosorbent assay every 7 days for 49 days. BALB/c mice developed CAR bacillus-induced lesions early in the course of disease that became more severe with time. Correlating with increasing disease severity, BALB/c mice had elevations in all antibody isotypes tested, and elevations in pulmonary TNF-alpha, IFN-gamma, and IL-4. C57BL/6 mice developed mild lesions with mild increases in serum IgM, IgG1, IgG2b, and IgG3 levels and minimally detectable IgG2a and IgA. Cytokine perturbations were not detected in C57BL/6 mice. The persistence of infection in BALB/c mice with vigorous serum antibody responses and increased IFN-gamma and IL-4 responses suggests that humoral immunity and T-cell responses are ineffective at preventing CAR bacillus disease. Furthermore, the lackluster antibody responses and undetectable cytokine responses in C57BL/6 mice suggest that humoral immunity and T-cell responses are not critical in resistance to CAR bacillus-induced disease.     

Differential susceptibility to acute Trypanosoma cruzi infection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities

Inoculation of Trypanosoma cruzi, Tulahuén strain, into C57BL/6 and BALB/c mice led to an acute infection characterized by marked parasitaemia, myocardial inflammation and thymocyte depletion. While C57BL/6 mice showed a progressive and lethal disease, BALB/c mice partly recovered. To characterize these murine models more effectively, we studied the parasite burden, serum levels of major infection outcome-related cytokines, the in vitro features of T. cruzi infection in peritoneal macrophages and the immunophenotype of thymic cells. The greater disease severity of T. cruzi-infected C57BL/6 mice was not linked to an increased parasite load, as parasitaemia, myocardial parasite nests and amastigote counts in peritoneal macrophages were not different from those in BALB/c mice. Cortical thymocyte loss was accompanied by the presence of apoptotic bodies and fragmented nuclear DNA, whereas fluorocytometric analysis at 17 days postinfection (p.i.) revealed a more pronounced loss of CD4+ CD8+ cells in C57BL/6 mice. This group displayed higher levels of TNF-alpha on days 14 and 21 p.i., in the presence of lower IL-1beta and IL-10 concentrations by days 14 and 21, and days 7 and 14 p.i., respectively. Day-21 evaluation showed higher concentrations of nitrate and TNF-alpha soluble receptors in C57BL/6 mice with no differences in IFN-gamma levels, with respect to the BALB/c group. Increased morbidity of C57BL/6 T. cruzi-infected mice does not seem to result from an aggravated infection but from an unbalanced relationship between pro- and anti-inflammatory mediators.     

Acute Immune Response to Mycobacterium massiliense in C57BL/6 and BALB/c Mice

Mycobacterium massiliense is an environmental opportunistic pathogen that has been associated with soft tissue infection after minor surgery. We studied the acute immune response of C57BL/6 and BALB/c mice infected intravenously with 10⁶ CFU of an M. massiliense strain isolated from a nosocomial infection in Brazil. The results presented here show that M. massiliense is virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells, and natural killer cells induced by gamma interferon and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice.Mycobacteria that do not belong to the complex Mycobacterium tuberculosis are known as nontuberculous mycobacteria (NTM) or atypical mycobacteria. NTM are ubiquitous microorganisms found worldwide in soil and water (3, 23, 38). These environmental mycobacteria are considered emerging and environmental opportunistic pathogens (6, 23).Mycobacterium massiliense is an environmental nonphotochromogenic, rapidly growing Mycobacterium strain that has been associated with soft-tissue infection after minor surgery or intramuscular injection (3, 5, 17, 22, 26, 46) and with pulmonary infection due to diseases, such as cystic fibrosis (29, 41). This species differs only slightly from Mycobacterium abscessus, sharing a 99.6% sequence identity of their 16S rRNA genes; genetic differences can be observed by comparative sequence analysis of the rpoB and hsp65 genes (1, 25, 42). Infections with these agents tend to respond poorly to macrolide-based chemotherapy (3), even though the organisms are susceptible to clarithromycin (15, 44, 47).M. massiliense infection mainly affects immunocompetent individuals and occasionally is associated with disseminated disease (8). An outbreak of M. massiliense occurred in Goiania, Brazil, where 30 individuals were infected after undergoing knee joint and laparoscopic surgery (5). Despite the fact that the infected individuals were from different hospitals, a unique M. massiliense strain was identified and characterized by pulsed-field gel electrophoresis.Disease pathogenesis involves host-pathogen interactions that directly affect parasite clearance. Typically, when environmental bacteria are passively introduced into the host, rapid bacterial clearance occurs due to an efficient innate immune response (30). Nonetheless, accidental infections with M. massiliense have been described as having a chronic evolution and, in some cases, the disease is disseminated irrespective of the host''s immune status. Such findings raise the possibility that this species is more virulent and/or pathogenic than other environmental mycobacteria, such as M. chelonae and M. abscessus.Recently, a murine model of M. abscessus infection was described, and isogenic mice were shown to be good models to address the immune response of the host (34, 39). In the present study, we analyzed the immune response of C57BL/6 and BALB/c mice infected with a clinical isolate of M. massiliense obtained from the recent outbreak in Goiania, Brazil. We show here that M. massiliense is virulent and pathogenic to both C57BL/6 and BALB/c mice, inducing a granulomatous inflammatory reaction that involves the activation of macrophages, dendritic cells (DCs), and natural killer (NK) cells induced mainly by gamma interferon (IFN-γ) and interleukin-17 (IL-17) in C57BL/6 mice and by IL-12 in BALB/c mice.     

Enhanced susceptibility to MPTP neurotoxicity in magnesium-deficient C57BL/6N mice

We evaluated the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6N mice fed a magnesium (Mg(2+))-deficient diet. On the 3rd week, Mg(2+)-deficient mice displayed increased anxiety- and depression-like behavior. In the Mg(2+)-deficient mice, a low does (10mg/kg) of MPTP treatment decreased dopamine (DA) and its metabolites contents in the striatum, but not in control mice. The same dose of MPTP did not influence these neurochemical markers in the mice fed Mg(2+)-deficient diet for 1 week which did not exhibit the altered emotional behavior. These results indicate that Mg(2+)-deficient mice with altered emotional behavior appear to increase the susceptibility to MPTP neurotoxicity in C57BL/6N mice.     

Vitamin A metabolism and mucosal immune function are distinct between BALB/c and C57BL/6 mice

The vitamin A metabolite retinoic acid (RA) has been reported to suppress Th1 responses and enhance Th2 responses. Here, we investigated whether differences in vitamin A metabolism could underlie the differences between C57BL/6 and BALB/c mice, which are reportedly seen as Th1 and Th2 responders, respectively. BALB/c mice were shown to have higher intestinal epithelial expression of RALDH1 (where RALDH is retinaldehyde dehydrogenase), and, consequently, higher RALDH activity in MLN‐DCs, leading to an increased ability to induce IgA class switching in B cells. Furthermore, within BALB/c mice, induction of IgA secretion as well as increased accumulation of regulatory T cells (Treg) in the intestinal lamina propria was observed. Additionally, as BALB/c mice are more resistant to dextran sulphate sodium (DSS) induced colitis, mice that lacked vitamin A in their diet had a more severe form of DSS‐induced colitis compared to control mice. Therefore, the level of RA production and consequently the degree of RA‐mediated signaling is crucial for the efficiency of the mucosal immune system.     

牛MBP诱导BALB/c和C57BL/6小鼠实验性变态性脑脊髓炎样反应的研究

为了进一步研究实验性变态反应性脑脊髓炎(EAE)动物模型,采用从新鲜牛脊髓中提取的MBP免疫诱导非敏感品系BALB/c小鼠和C57BL/6小鼠,通过对实验动物的症状、中枢神经系统的病理改变及细胞因子水平变化的检测,较成功地建立了C57BL/6、BALB/c小鼠的EAE模型,实验方法稳定可靠。     

Differential mechanisms of resistance to sublethal systemic Aspergillus fumigatus infection in immunocompetent BALB/c and C57BL/6 mice

Studies of systemic and pulmonary Aspergillus fumigatus infection demonstrated differential susceptibility of inbred mice of various genetic background to lethal outcome, with an opposite pattern of Th1 cytokine interferon-γ (IFN-γ) and Th2 cytokine interleukin-4 (IL-4) in susceptible vs resistant mice. We have shown recently reciprocal IFN-γ and IL-4 expression in spleens of Th1-prone C57BL/6 mice in sublethal systemic aspergillosis. In this study, resistance to systemic (i.v.) A. fumigatus infection was investigated in Th2-prone BALB/c mice by survival rate at different fungal inocula, efficiency of reduction of visceral organ and spleen fungal burden at sublethal conidia dose and splenic immune response to this dose and compared to C57BL/6 mice. No strain differences in survival were noted at three A. fumigatus doses, with similar extent and dynamics of fungal eradication from all organs following sublethal conidia dose injection. Progressive decrease in spleen fungal burden was associated with different dynamics and quality of changes in spleen activity of BALB/c and C57BL/6 mice. Increased spleen mass and cellularity was noted in both strains, with higher values in BALB/c mice at some time points what might be ascribed to peripheral blood cell recruitment, as well as hematopoietic activity and red pulp upgrowth. Infection tipped the balance towards pro-inflammatory antifungal splenic response by a highly increasing IFN-γ and without changing the IL-4 expression in BALB/c mice, in contrast to down-regulating anti-inflammatory (IL-4) and a moderately increasing IFN-γ response in C57BL/6 mice. Jointly, stimulation of IL-17 expression noted in both strains provided an optimal inflammatory milieu in the spleen of infected mice that might have contributed to efficient removal of conidia.     

Morphofunctional characteristic of the immune system in BALB/c and C57BL/6 mice

Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.     

自主运动后BALB/c和C57BL/6小鼠学习记忆行为学指标的分析比较

BACKGROUND: BALB/c and C57BL/6 mice are two inbred strains, but after voluntary movement, there is no report on how to scientifically reasonably select behavioral experiment methods and indicators and to evaluate the learning and memory abilities of mice.     

Distinct granuloma responses in C57BL/6J and BALB/cByJ mice in response to pristane

Granuloma formation is an inflammatory response of the host against invading pathogens or indigestible substances. We generated mesenteric oil granulomas by injecting pristane into the peritoneal cavity (PC) of mice, and compared oil granuloma formation in the C57BL/6J and BALB/cByJ strains of mice. The formation and kinetics of oil granulomas were distinct between the two strains. In C57BL/6J mice, injected pristane induced oil granuloma formation at both the mesenteric centers (MG) and margins (SG). MG was resolving by 11 weeks, and SG persisted. In BALB/cByJ mice, MG developed slower but persisted longer than in C57BL/6J mice, and SG resolved sooner than in C57BL/6J mice. Injection of India ink revealed that phagocytes were localised mainly to the SG in C57BL/6J mice, but were located diffusely in both MG and SG of BALB/cByJ mice. SG cells expressed more monocyte chemotactic protein‐1 (MCP‐1) mRNA than MG cells in C57BL/6J mice, but there was no difference in MCP‐1 expression between the MG and SG in BALB/cByJ mice. These observations suggest that the recruitment of inflammatory leucocytes under the direction of chemokines differentiates the patterns of granuloma responses to pristane in C57BL/6J and BALB/cByJ mice.     

High frequency mechanical ventilation affects respiratory system mechanics differently in C57BL/6J and BALB/c adult mice

We tested the hypothesis that high frequency ventilation affects respiratory system mechanical functions in C57BL/6J and BALB/c mice. We measured respiratory mechanics by the forced oscillation technique over 1 h in anesthetized, intubated, ventilated BALB/c and C57BL/6J male mice.