Showing papers on "BALB/c published in 2005"

Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation

Abstract: Exposure to dextran sulfate sodium (DSS) induces acute colitis, which is normally resolved after DSS removal. To study chronicity, mice are typically subjected to three to five cycles of weekly DSS exposures, each followed by a 1- to 2-wk rest period. Here, we describe a novel and convenient way of inducing chronic, progressive colitis by a single exposure to DSS. C57BL/6 mice exposed to DSS for 5 days developed acute colitis that progressed to severe chronic inflammation. The plasma haptoglobin levels remained high during the chronic phase, showing that the inflammation was active. Surprisingly, the mice regained their original weight along with the progression of colitis, and the only apparent symptom was loose feces. Histopathological changes 4 wk after DSS removal were dense infiltrates of mononuclear cells, irregular epithelial structure, and persistent deposits of collagen. A progressive production of the cytokines IL-1β, IL-12 p70, and IL-17 correlated with the extensive cellular infiltration, whereas high IFN-γ production was mainly found late in the chronic phase. Similar to C57BL/6 mice, BALB/c mice exposed to 5 days of DSS developed acute colitis as previously described. The acute colitis was accompanied by elevated plasma levels of haptoglobin and increased colonic levels of IL-1α/β, IL-6, IL-18, and granulocyte colony-stimulating factor. However, soon after DSS removal, BALB/c mice recovered and were symptom free within 2 wk and completely recovered 4 wk after DSS removal in terms of histopathology, haptoglobin levels, and local cytokine production. In summary, these data stress the effect of genetic background on the outcome of DSS provocation. We believe that the present protocol to induce chronic colitis in C57BL/6 mice offers a robust model for validating future therapies for treatment of inflammatory bowel disease.

IFN-α Induces Early Lethal Lupus in Preautoimmune (New Zealand Black × New Zealand White)F1 but Not in BALB/c Mice

Abstract: Recent studies indicate that IFN-α is involved in pathogenesis of systemic lupus erythematosus. However, direct proof that IFN-α is not only necessary, but also sufficient to induce lupus pathogenicity is lacking. In this study, we show that in vivo adenovector-mediated delivery of murine IFN-α results in preautoimmune (New Zealand Black (NZB) × New Zealand White (NZW))F 1 , but not in normal, mice, in a rapid and severe disease with all characteristics of systemic lupus erythematosus. Anti-dsDNA Abs appeared as soon as day 10 after initiation of IFN-α treatment. Proteinuria and death caused by glomerulonephritis occurred in all treated mice within, respectively, ∼9 and ∼18 wk, at a time when all untreated (NZB × NZW)F 1 did not show any sign of disease. IFN-α in vivo induced an overexpression of B lymphocyte stimulator in circulation at similar levels in both the preautoimmune and the normal mouse strains. All effects elicited by IFN-α were dose dependent. (NZB × NZW)F 1 infused with purified murine IFN-α also showed acceleration of lupus. Thus, prolonged expression of IFN-α in vivo induces early lethal lupus in susceptible animals.

BALB/c mice have more CD4+CD25+ T regulatory cells and show greater susceptibility to suppression of their CD4+CD25− responder T cells than C57BL/6 mice

Abstract: Increasing evidence indicates that CD4(+)CD25(+) T regulatory (Treg) cells control a wide spectrum of immune responses. The initial identification of CD4(+)CD25(+) Treg cell as a "professional suppressor" was based on observations made in BALB/c mice. This mouse strain is well known to preferentially develop T helper cell type 2 responses, to be more susceptible to intracellular parasite infection, to have a higher tumor incidence, and to be more resistant to the induction of autoimmune diseases, as compared with C57BL/6 (B6) mice. We therefore decided to compare Treg cell function of B6 and BALB/c mice. We observed that the frequency of CD4(+)CD25(+) T cells in the thymus and peripheral lymphoid organs of BALB/c mice was higher than in B6 mice. CD4(+)CD25(+) Treg cells from both mouse strains shared similar phenotypic properties, including expression of characteristic immunological markers and hyporesponsiveness to T cell receptor cross-linking and in their capacity to suppress proliferation of BALB/c CD4(+)CD25(-) T responder (Tres) cells. However, CD4(+)CD25(-) Tres cells from B6 mice were notably less susceptible to suppression by CD4(+)CD25(+) Treg cells from either mouse strain. Our data suggest that the number and the level of suppression of CD4(+)CD25(+) Treg cells for CD4(+)CD25(-) Tres cells may be dictated by genetic background. Our data also suggest that differences in the CD4(+)CD25(+) Treg cell number and the susceptibility of CD4(+)CD25(-) Tres cells may, at least in part, account for the differences in immune response between B6 and BALB/c strains of mice.

Peanut- and cow's milk-specific IgE, Th2 cells and local anaphylactic reaction are induced in Balb/c mice orally sensitized with cholera toxin

Abstract: Background: The development of animal models developing specific immunoglobulin (Ig)E presenting the same specificity as human IgE and similar clinical symptoms as those observed in allergic patients are of great interest for the understanding of mechanisms involved in the induction and regulation of food allergy. Methods: Balb/c female mice were sensitized with whole peanut protein extract (WPPE) by means of intraperitoneal (i.p.) injections with alum or gavages with cholera toxin (CT). The WPPE specific IgE, IgG1 and IgG2a were monitored. Th2 cells activation was analysed assaying interleukin (IL)-4 and IL-5 vs IFNγ on reactivated splenocytes. Local anaphylactic reaction was evaluated by assaying histamine in faecal samples. The oral sensitization protocol was further extended to cow's milk proteins (CMP). Results: Balb/c mice developed high peanut-specific IgE and IgG1 responses either after i.p. or oral sensitizations. In both cases, antibodies were specific to polymer of glycinin fragments, containing polypeptides from Ara h3/4, and to a lesser extent to Ara h1 and Ara h2. Interleukin-4 and IL-5 production were evidenced. Balb/c mice could also be sensitized to CMP, as demonstrated by CMP-specific IL-4 and IL-5 secretions and induction of IgE specific for whole caseins, β-lactoglobulin, serum bovine albumin and lactoferrin. Of interest was the occurrence of a local anaphylactic reaction in the peanut and CM models. Conclusions: In contrast with previous authors, Balb/c mice were sensitized and evidenced an allergic reaction after oral administrations of peanut or CMP plus CT, providing an interesting model for further studies on immunopathogenic mechanisms.

Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats.

Abstract: Human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family causing acute respiratory tract infections, especially in young children. We studied the pathogenesis of this viral infection in two experimental small animal models (BALB/c mice and cotton rats). Significant viral replication in the lungs of both animals was found following an intranasal challenge of 108 50% tissue culture infectious doses (TCID50) and persisted for <2 and <3 weeks in the case of cotton rats and mice, respectively. Peak viral loads were found on day 5 postinfection in both mice (mean of 1.92 × 107 TCID50/g lung) and cotton rats (mean of 1.03 × 105 TCID50/g). Clinical symptoms consisting of breathing difficulties, ruffled fur, and weight loss were noted in mice only around the time of peak viral replication. Most significant pulmonary inflammatory changes and peak expression of macrophage inflammatory protein 1α, gamma interferon, and RANTES occurred at the time of maximal viral replication (day 5) in both models. Cellular infiltration occurred predominantly around and within alveoli and persisted for at least 21 days in mice, whereas it was more limited in time with more peribronchiolitis in cotton rats. Both animal models would be of great value in evaluating different therapeutic agents, as well as vaccine candidates against hMPV.

Induction of systemic and mucosal cross-clade neutralizing antibodies in BALB/c mice immunized with human immunodeficiency virus type 1 clade A virus-like particles administered by different routes of inoculation.

Abstract: We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model, based on virus-like particles (VLPs) expressing gp120 from a Ugandan HIV-1 isolate of clade A (HIV-VLPAs), which shows the induction of neutralizing antibodies as well as cytotoxic T lymphocytes (CTL) in BALB/c mice by intraperitoneal (i.p.) administration. In the present study, immunization experiments based on a multiple-dose regimen have been performed with BALB/c mice to compare different routes of administration. i.p. and intranasal (i.n.), but not oral, administration induce systemic as well as mucosal (vaginal and intestinal) immunoglobulin G (IgG) and IgA responses. These immune sera exhibit >50% ex vivo neutralizing activity against both autologous and heterologous primary isolates. Furthermore, the administration of HIV-VLPAs by the i.n. immunization route induces a specific CTL activity, although at lower efficiency than the i.p. route. The HIV-VLPAs represent an efficient strategy to stimulate both arms of immunity; furthermore, the induction of specific humoral immunity at mucosal sites, which nowadays represent the main port of entry for HIV-1 infection, is of great interest. All these properties, and the possible cross-clade in vivo protection, could make these HIV-VLPAs a good candidate for a mono- and multicomponent worldwide preventive vaccine approach not restricted to high-priority regions, such as sub-Saharan countries.

Porcine Circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice

Abstract: We have previously described microscopic and electron microscopic alterations in lymphoid organs of PCV2 inoculated mice as apoptosis. In this study we wanted to investigate the molecular pathogenetic mechanism of PCV2-induced apoptosis. Eight-week old BALB/c mice were either sham inoculated (control mice) or inoculated intraperitoneally (ip) and intranasally (in) with a single (sPCV mice) or multiple (mPCV mice) doses of PCV2. Four control mice and 4 sPCV mice were sacrificed 7, 14, 28 and 42 days post inoculation (PI). All 4 mPCV mice were sacrificed 42 days PI. Following necropsy, immunohistochemistry for caspase 3 and in-situ TUNEL assay were performed on sections of spleen, lymph nodes, thymus and ileum from control, sPCV and mPCV mice. In addition, total RNA was extracted from spleens of control, sPCV and mPCV mice for simultaneous detection and semiquantitation of bcl-2 homologues and various caspase mRNAs using a multiprobe RNase protection assay system. PCV2 replicated and was associated with apoptosis in spleens, lymph nodes and Peyer's patches of infected BALB/c mice. Upregulation of caspase 1, 2, 3, 6, 7, 8, 11 and 12 and upregulation for the transcripts of apoptosis inhibitors bcl-2, bcl-w and bcl-X and apoptosis promoters' bax, bak and bad was detected in spleens of sPCV and mPCV mice, but not control mice. Apoptosis was further confirmed by light and electron microscopic morphology as well as by positive TUNEL assay and detection of activated caspase 3. PCV2 nucleic acid was detected by in-situ hybridization in the nuclei and cytoplasm of such apoptotic cells. The data presented here support the hypothesis that PCV2 induces apoptosis mediated through the activation of caspases 8 and 3 in the spleens of infected mice.

Intramuscular immunization with p36(LACK) DNA vaccine induces IFN-γ production but does not protect BALB/c mice against Leishmania chagasi intravenous challenge

Abstract: Acute visceral leishmaniasis is a progressive disease caused by Leishmania chagasi in South America. The acquisition of immunity following infection suggests that vaccination is a feasible approach to protect against this disease. Since Leishmania homologue of receptors for activated C kinase (LACK) antigen is of particular interest as a vaccine candidate because of the prominent role it plays in the pathogenesis of experimental Leishmania major infection, we evaluated the potential of a p36(LACK) DNA vaccine in protecting BALB/c mice challenged with L. chagasi. In this study, mice received intramuscular (i.m.) or subcutaneous (s.c.) doses of LACK DNA vaccine. We evaluated the production of vaccine-induced cytokines and whether this immunization was able to reduce parasite load in liver and spleen. We detected a significant production of interferon gamma by splenocytes from i.m. vaccinated mice in response to L. chagasi antigen and to rLACK protein. However, we did not observe a reduction in parasite load neither in liver nor in the spleen of vaccinated animals. The lack of protection observed may be explained by a significant production of IL-10 induced by the vaccine.

Vaccination with the Leishmania infantum acidic ribosomal P0 protein plus CpG oligodeoxynucleotides induces protection against cutaneous leishmaniasis in C57BL/6 mice but does not prevent progressive disease in BALB/c mice.

Abstract: We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on the Leishmania infantum acidic ribosomal protein P0 (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L. major parasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces the L. major infection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-γ) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-γ in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced by L. major infection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.

Inflammatory cell infiltration and high antibody production in BALB/c mice caused by natural exposure to Lutzomyia longipalpis bites.

Abstract: Sand flies inject saliva into the mammalian host when probing for a blood meal. Understanding the initial vertebrate reactions against sand fly saliva is important for possible interventions because these insects transmit diseases to humans and other animals. Little is known of these reactions to New World sand flies. Repeated exposure of BALB/c mice to Lutzomyia longipalpis bites leads to local inflammatory cell infiltration comprised of neutrophils, macrophages, and eosinophils. Total IgG and IgG1 antibodies react predominantly with three major protein bands (45, 44, and 16 kD) of the insect saliva by Western blot. The injection of immune serum previously incubated with salivary gland homogenate induced an early infiltration with neutrophils and macrophages, suggesting the participation of immune complexes in triggering inflammation.

Control of Infection with Leishmania major in Susceptible BALB/c Mice Lacking the Common γ-Chain for FcR Is Associated with Reduced Production of IL-10 and TGF-β by Parasitized Cells

Abstract: Previous studies have shown that the in vitro ligation of FcgammaRs with IgG-opsonized Leishmania amastigotes promotes IL-10 production by macrophages. In addition, infection of either BALB/c mice lacking the common gamma-chain of Fc receptors (FcgammaR(-/-)) or mice genetically altered to lack circulating Ab (J(H)D) with Leishmania pifanoi results in reduced and delayed lesion development and a deficit in the recruitment of inflammatory cells into infected lesions. We show in this study that FcgammaR(-/-) mice can control infection with Leishmania major and totally resolve cutaneous lesions. The ability to eventually control infection is not associated with a reduction in lesion inflammation or a reduction in the ability of Leishmania to parasitize cells through week 6 of infection. The immune response in healing FcgammaR(-/-) mice is associated with a reduction in numbers of cells producing Th2-type cytokines, including IL-4 and IL-10, but not an increase in numbers of IFN-gamma-producing cells characteristic of a dominant Th1-type response. Instead, we observe a reduction in levels of IL-10 and TGF-beta within infected lesions, including reduced levels of these cytokines within parasitized macrophages. Together, these results suggest that uptake of opsonized parasites via FcgammaRs may be a strong in vivo stimulus for the production of anti-inflammatory cytokines that play a role in susceptibility to infection.

Persistent airway hyper-responsiveness and inflammation in Toxocara canis- infected BALB/c mice

Abstract: BACKGROUND: Infection with Toxocara canis, the roundworm of dogs, has been associated with asthmatic manifestations. Clinical symptoms such as wheezing, coughing and episodic airflow obstruction have been described for patients infected with this helminth. OBJECTIVE: In order to characterize the effect of T. canis infection on the lungs, we monitored immune responses, pulmonary pathology and lung function over a period of 60 days in BALB/c mice. METHODS: Infection was performed by a single oral administration of 1000 T. canis embryonated eggs. Airway responsiveness was measured in conscious, unrestrained mice at 7, 14, 30 and 60 days post-infection (p.i.). RESULTS: Infection of mice resulted in airway hyper-responsiveness (AHR) that persisted up to 30 days p.i. Pulmonary inflammation as well as increased levels of IgE and eosinophils in bronchoalveolar lavage (BAL) persisted up to 60 days p.i. Cytokine analysis in BAL indicated increased levels of IL-5 at day 7 and 14 p.i., whereas the levels of IL-2, IFN-gamma, IL-4 and IL-10 did not differ from those of uninfected controls. Toxocara-specific stimulation of spleen cells using recombinant TES-70 protein resulted in the induction of IL-5 at day 7 and 14 p.i. and IL-10 at day 14 p.i. Production of all other cytokines did not differ from that of uninfected controls. Evaluation of larval burden revealed that T. canis was still present in the lungs of infected mice at 60 days p.i. CONCLUSION: The presence of Toxocara larva in the lungs at 60 days p.i. following a single infection could explain the persistent pulmonary inflammation, airway hyper-reactivity, eosinophilia and increased IgE production observed in T. canis-infected BALB/c mice.

Importance of CD8+Vβ8+ T Cells in IFN-γ-Mediated Prevention of Toxoplasmic Encephalitis in Genetically Resistant BALB/c Mice

Abstract: In our attempt to identify a major T cell population(s) that recognizes protective Toxoplasma gondii antigens and produces interferon-gamma (IFN-gamma) for prevention of toxoplasmic encephalitis (TE), we found T cell receptor Vbeta8(+) cells to be the most frequent IFN-gamma-producing population infiltrated into the brain of T. gondii-infected BALB/c mice genetically resistant to the disease. To examine the role of IFN-gamma production by this T cell population for resistance, we transferred Vbeta8(+) immune T cells purified from spleens of infected BALB/c and IFN-gamma(/) mice into infected, sulfadiazine-treated, athymic nude mice. After discontinuation of sulfadiazine treatment, control nude mice that had not received any T cells and animals that had received Vbeta8(+) T cells from IFN-gamma(/) mice all died because of reactivation of infection (TE). In contrast, animals that had received the cells from BALB/c mice survived. Thus, IFN-gamma production by Vbeta8(+) T cells plays an important role in prevention of TE in these animals. When Vbeta8(+) immune T cells were divided into CD4(+) and CD8(+) subsets, a potent protective activity was observed only in the CD8(+) subset, whereas a combination of both subsets provided greater protection than did the CD8(+)Vbeta8(+) population alone. These results indicate that the CD8(+) subset of Vbeta8(+) T cells is a major afferent limb of IFN-gamma-mediated resistance of BALB/c mice against TE, although the CD4(+) subset of the T cell population works additively or synergistically with the CD8(+)Vbeta8(+) population.

Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice

Abstract: Because most autoimmune diseases are polygenic, analysis of the synergistic involvement of various immune regulators is essential for a complete understanding of the molecular pathology of these diseases. We report the regulation of autoimmune diseases by epistatic effects of two immunoinhibitory receptors, low affinity type IIb Fc receptor for IgG (FcgammaRIIB) and programmed cell death 1 (PD-1). Approximately one third of the BALB/c-Fcgr2b(-/-)Pdcd1(-/-) mice developed autoimmune hydronephrosis, which is not observed in either BALB/c-Fcgr2b(-/-) or BALB/c-Pdcd1(-/-) mice. Hydronephrotic mice produced autoantibodies (autoAbs) against urothelial antigens, including uroplakin IIIa, and these antibodies were deposited on the urothelial cells of the urinary bladder. In addition, approximately 15% of the BALB/c-Fcgr2b(-/-)Pdcd1(-/-) mice produced antinuclear autoAbs. In contrast, the frequency of the autoimmune cardiomyopathy and the production of anti-parietal cell autoAb, which were observed in BALB/c-Pdcd1(-/-) mice, were not affected by the additional FcgammaRIIB deficiency. These observations suggest cross talk between two immunoinhibitory receptors, FcgammaRIIB and PD-1, on the regulation of autoimmune diseases.

Characterization of the B-cell immune response elicited in BALB/c mice challenged with Neospora caninum tachyzoites.

Abstract: Activation of B cells occurring in hosts infected with protozoan parasites has been implicated either in protective or parasite-evasion immune-mediated mechanisms. Intraperitoneal inoculation of Neospora caninum tachyzoites into BALB/c mice induces an acute response characterized by a rapid increase in the numbers of CD69-expressing peritoneal and splenic B cells. This early B-cell stimulatory effect preceded an increase in the numbers of total and immunoglobulin-secreting splenic B cells and a rise in serum levels of N. caninum-specific immunoglobulins, predominantly of the immunoglobulin G2a (IgG2a) and IgM isotypes. Increased numbers of B cells expressing the costimulatory molecules CD80 and CD86 were also observed in the N. caninum-infected mice. The B-cell stimulatory effect observed in mice challenged with N. caninum tachyzoites was reduced in mice challenged with gamma-irradiated parasites. Contrasting with the peripheral B-cell expansion, a depletion of B-lineage cells was observed in the bone-marrow of the N. caninum-infected mice. Intradermal immunization of BALB/c mice with diverse N. caninum antigenic preparations although inducing the production of parasite-specific antibodies nevertheless impaired interferon-gamma (IFN-gamma) mRNA expression and caused lethal susceptibility to infection in mice inoculated with a non-lethal parasitic inoculum. This increased susceptibility to N. caninum was not observed in naive mice passively transferred with anti-N. caninum antibodies. Taken together, these results show that N. caninum induces in BALB/c mice a parasite-specific, non-polyclonal, B-cell response, reinforce previous observations made by others showing that immunization with N. caninum whole structural antigens increases susceptibility to murine neosporosis and further stress the role of IFN-gamma in the host protective immune mechanisms against this parasite.

Increased susceptibility of male BALB/c mice to coxsackievirus B3-induced myocarditis: role for CD1d.

Abstract: BALB/c male mice infected with the H3 variant of coxsackievirus B3 (CVB3) develop fulminant myocarditis. Age-matched female mice show little myocarditis due to decreased virus receptor expression on cardiac cells. TNFα and IL-1β levels were increased in males by 3 days after infection. IFNγ levels increased more slowly throughout the 7-day observation period. CD4+, CD8+, macrophage (Mac3+) and γδ+ cells all accumulated in male hearts, with γδ+ cells showing early (day 3) infiltration. Females also accumulated CD4+ cells, but few of the other cell types. CD4+ cells in male hearts predominately produced IFNγ, indicating a Th1 cell phenotype, whereas CD4+ cells in females produced IL-4, but little IFNγ, indicating a Th2 phenotype. CD1d, a major histocompatibility complex I-like molecule often implicated in innate immunity, was increased in CVB3-infected male but not female cardiocytes both in vivo and in vitro. These results demonstrate that CVB3 infections produce gender-specific differences in both innate and adaptive immunity, which may explain the difference in disease susceptibility.

Gastric Pit Cell Hyperplasia and Glandular Atrophy in Carbonic Anhydrase IX Knockout Mice: Studies on Two Strains C57/BL6 and BALB/C

Abstract: Carbonic anhydrase (CA) isoenzyme IX is a hypoxia-inducible enzyme, which is expressed in the human and rodent gastrointestinal tract and overexpressed in several different tumors. Functionally, it has probably an effect on proliferation and differentiation of gastrointestinal epithelial cells. It may also participate in gastric morphogenesis, since a recent study has shown gastric pit cell hyperplasia and glandular atrophy in CA IX-knockout mice. However, it is not known whether CA IX produces morphological changes in the gastric mucosa, which can turn into a dysplasia or malignancy in the presence of some carcinogenic factors. High-salt diet is considered such a factor which has been shown to modulate Helicobacter pylori-associated carcinogenesis. We produced two strains of CA IX-knockout mice, C57/BL6 and BALB/c, and the mice ate either standard or high-salt feed for 20 weeks. Stomach samples were collected from 40 Car9−/− knockout mice and 37 wildtype littermates, and the tissue sections were examined for histology. CA IX-deficiency caused gastric pit cell hyperplasia and glandular atrophy in both BALB/c and C57/BL6 strains. Excess dietary salt had no significant effect on the severity of pit cell hyperplasia. No dysplasia was found in any of the groups. In C57/BL6 mice, CA IX-deficiency was associated with gastric submucosal inflammation. The results indicate that CA IX-deficiency provides a useful model to study the mechanisms of gastric morphogenesis and epithelial integrity. Further studies are needed to see whether CA IX has a role in the regulation of immune response. The findings suggest that although CA IX-deficiency is not a tumor-promoting factor per se, it induces glandular atrophy in the body mucosa, a lesion which is considered to be a preneoplastic alteration in the stomach.

Non-sand fly transmission of a north american isolate of leishmania infantum in experimentally infected balb/c mice

Abstract: Leishmania infantum, an etiologic agent of zoonotic visceral leishmaniasis, is endemic in the foxhound population in the United States and Canada. Leishmaniasis is usually transmitted by blood-feeding sand flies; however, epidemiological data do not support a significant role for sand flies in the maintenance of foxhound infections in North America, and an alternate mode of transmission may exist. The present study was conducted to determine if transplacental or direct transmission occurs in pregnant BALB/c mice experimentally infected with L. infantum isolated from a naturally infected foxhound from Virginia as well as to determine if the parasite was directly transmitted to the males used to breed the mice. Female BALB/c mice were intravenously inoculated with 1 × 106 promastigotes of the LIVT-1 strain of L. infantum. Mice were bred to uninfected male BALB/c mice 2 mo postinoculation. Pregnant mice were killed between days 13 and 18 of gestation. Pups and placentas were collected at necropsy, divided, a...