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1.
Use of a murine xenograft model for canine transmissible venereal tumor   总被引：1，自引：0，他引：1  
OBJECTIVE: To develop a murine model for canine transmissible venereal tumor (CTVT). ANIMALS: Thirty-three 6-week-old NOD/LtSz-scid (NOD/SCID) mice and seven 6-week-old C57BL/6J mice. PROCEDURE: Samples of CTVT were excised from a 3-year-old dog and inoculated SC into ten 6-week-old NOD/SCID mice to induce growth of xenograft transmissible venereal tumor (XTVT). To establish mouse-to-mouse transmission, samples of XTVT were removed and inoculated SC into 4 groups of 6-week-old NOD/SCID mice and into a control group. Samples of CTVT were also inoculated into immunocompetent C57BL/6J mice for a mouse antibody production (MAP) test. The canine and xenografted tumors were evaluated cytologically and histologically, and polymerase chain reaction was performed for detection of the rearranged LINE/c-MYC junction. RESULTS: 8 of 10 NOD/SCID mice that were inoculated with CTVT developed tumors 3 to 10 weeks after inoculation. In the second-generation xenograft, all mice developed tumors by postinoculation day 47; 1 X 10(6) of XTVT cells were enough to create a xenograft. Metastases developed in 4 of 20 mice. Xenografted and metastatic tumors retained cytologic, histologic, and molecular characteristics of CTVT. Results of the MAP test were negative for all pathogens. CONCLUSION: We established an NOD/SCID murine model for XTVT and metastasis of CTVT. This model should facilitate study of tumor transplantation, progression, and metastasis and should decrease or eliminate the need for maintaining allogenic transfer in dogs.  相似文献   

2.
Canine transmissible venereal tumor (CTVT) is primarily a tumor of adult dogs with a high incidence of spontaneous regression. We recently reported a xenograft model of CTVT (XTVT) in NOD/SCID mice. XTVT cells retain cytological and histological features of CTVT as well as characteristic rearranged LINE/c-MYC junction [Am. J. Vet. Res. 62 (2001) 907]. In this paper, we demonstrate that XTVT cells maintain ultrastructural characteristics of CTVT and do not express MHC classes I and II molecules.  相似文献   

3.
The prevailing paradigm is that immunosuppressed individuals are more susceptible to infection and are at higher risk of infection from Cryptosporidium oocysts if present in drinking water. To test this hypothesis, three immune conditions were examined: genetically immunocompromised T cell deficient CD-1 nude mice, B and T cell deficient Fox Chase CB-17/IcrClB SCID mice, and chemically immunosuppressed C57Bl/6 mice. Chemical immunosuppression was induced with a single subcutaneous injection of methylprednisolone acetate (MPA) at 600 mg/kg. The MPA immunosuppressed C57Bl/6 mice were characterized by a sustained decrease in circulating CD3, CD4 and CD8 T-lymphocytes of greater than 80% and a similar decrease in B-lymphocytes. A sharp rise in circulating mature segmented neutrophils followed MPA injection, dropping sharply after 10-14 days, mirroring the decrease in lymphocytes. The cessation of oocyst production after MPA was not accompanied by a radical rise in circulating CD3 or CD4 T-lymphocytes, but rather a rise in CD8 T-lymphocytes. The ID50 for the MPA immunosuppressed C57Bl/6 mice was 122 oocysts, whereas the ID50 for the C57Bl/6 immunocompetent group was 44. The genetically immunocompromised mice showed similar differences. The ID50 for CD-1 nude mice was 166 oocysts compared to 64 in CD-1 immunocompetent mice. For Fox Chase CB-17/IcrClB SCID and the immunocompetent CB-17 mice, the ID50's were 83 and 60 oocysts, respectively. These results suggest that the lack of an immune response does not increase the ability of C. muris to establish a productive infection and produce oocysts.  相似文献   

4.
Background: Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor‐initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B‐cell lymphoma have not been conclusively identified. Hypothesis/Objectives: Tumor cells with a progenitor phenotype exist in B‐cell lymphoma, reflecting a hierarchical organization. Animals: Twenty‐eight client‐owned dogs with previously untreated B‐cell lymphoma and 6 healthy dogs. Methods: This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B‐cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL‐2Rγ?/? mice was adapted to expand and serially transplant primary canine B‐cell lymphoma. Results: LPCs were expanded in lymph nodes from 28 dogs with B‐cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B‐cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed. Conclusions and Clinical Importance: These results suggest the presence of a hierarchy of tumor cells in B‐cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy.  相似文献   

5.
A study was conducted to establish baseline data on Brucella abortus infection induced in 5 strains of mice (CBA/NJ, BALB/c, CD-1, C3H/HeN, and C3H/HeJ). The strains were compared on the basis of immunologic, histopathologic, and bacteriologic responses. There were 4 treatment groups for each strain of mice: (1) vaccinated with homologous lipopolysaccharide and challenge exposed to B abortus strain 2308; (2) not vaccinated but challenge exposed; (3) vaccinated and not challenge exposed; and (4) not vaccinated and not challenge exposed. Results indicated that mice can be used for comparative studies on the pathogenesis and immunogenesis of B abortus infections; strains of mice may vary in their responses to Brucella infection, regardless of their vaccination status. Bacteriologic and immunologic responses in mouse strains BALB/c, CD-1, C3H/HeN, and C3H/HeJ, but not those of CBA/NJ, were extrapolative among strains.  相似文献   

6.
Morbillivirus infections have been responsible for mass mortalities in several species of marine mammals. Nevertheless, relatively little is known on the pathogenesis of the disease and the immune response to the agent, especially in cetaceans, hindering the treatment of individuals and the development of appropriate vaccines, given the difficulty of performing experimental work in marine mammals. The reconstitution of severe combined immunodeficient (SCID) mice, which do not have the ability to reject grafts, with lymphocytes from different species has been used with increasing success as a surrogate species model to study the immune system. We injected NOD/SCID mice with lymphocytes from different species of cetaceans and further vaccinated those mice with a commercial canine distemper virus (CDV) vaccine to develop a practical model to study cetacean immune response to a morbillivirus. Reconstitution was detected in 10/20 mice reconstituted with harbor porpoise spleen, 6/10 mice reconstituted with harbor porpoise lymph node cells, 8/10 mice reconstituted with fresh beluga PBMCs and none of the mice reconstituted with neonate bottlenose dolphin spleen or thymus cells when assessed 42-63 days after reconstitution. While a humoral immune response was detected in none of the reconstituted mice, a cell-mediated immune response to the CDV vaccine was detected in 6/15 (40%) and 2/18 (11%) of the SCID mice after reconstitution with cetacean immune cells after a single or booster vaccination, respectively, for a combined total of 8/33 (24%). This represents the first demonstration of successful reconstitution of SCID mice with marine mammal cells, and to the authors' knowledge, the first direct demonstration of a primary antigen-specific cell-mediated immune response in reconstituted SCID mice. This model will be useful for further research on the physiology of the marine mammal immune system and its response to infectious agents and vaccines, with possible important outcomes in conservation issues.  相似文献   

7.
Treatment of canine‐transmissible venereal tumour (CTVT) with local vascular‐targeted photodynamic therapy (VTP) using Pd‐bacteriopheophorbide (WST09) as a drug is suggested as an alternative to conventional chemotherapy. Male CD1 nude mice were subcutaneously grafted with the xenograft‐transmissible canine venereal tumour (XTVT). The VTP protocol delivered once consisted of intravenous administration of WST09 (10 mg kg?1) followed by immediate local illumination with a diode laser (763 nm). Controls included animals treated with light or WST09 alone. Macroscopic and microscopic evaluations of tumour response were conducted 10, 24 and 48 h after treatment. Upon VTP, tumours underwent necrosis that lasted 8–10 days and exhibited complete healing by 25–35 days, reaching an overall long‐term cure rate (83%) by 90 days after treatment. This study suggests that VTP with WST09 can efficiently treat CTVT in a single session, as compared with 4–6 sessions of chemotherapy and thus may be feasible for common veterinary practice, particularly under ambulatory conditions.  相似文献   

8.
Canine mast cell tumors (MCTs) are the most common cutaneous tumors in the dog. They have a wide range of behaviour, which can make these tumors challenging to treat. Recently, mutations in c-kit proto-oncogene have been identified in several canine MCTs. Imatinib is the first member of a new class of agents that act by inhibiting particular tyrosin kinase enzymes, including KIT which is a product of the c-kit. In this study the efficacy of imatinib to reduce or abolish canine MCT [CMC-1] using xenografted MCT in severe combined immunodeficient [SCID] mice was evaluated. Imatinib was administered at doses of 200 mg/kg and 100 mg/kg once a day for one week. The antitumor responses in SCID mice with CMC-1 xenografts following treatment with imatinib were observed. Significant tumor regression occurred with 100 mg/kg on days 7, 10, 14 and 21, and 200 mg/kg on all days. Our results indicate that imatinib is effective against canine mast cell tumor in mouse xenograft models. Canine MCTs might be a potential target for imatinib therapy.  相似文献   

9.
A study was made of the infectivity of two mouse-adapted strains of Cowdria ruminantium in mice. The Kwanyanga strain was most virulent in Balb/C mice which died nine days after infection with homogenate of liver from infected mice. CD-1 mice were least susceptible of six strains tested. The du Plessis strain of C. ruminantium was equally virulent in all six mouse strains. The du Plessis strain in CD-1 mice was used as the basis of a drug screen to detect activity against heartwater (C. ruminantium infection) and was highly predictive when active compounds were tested in sheep infected with the Ball 3 strain of C. ruminantium.  相似文献   

10.
Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.  相似文献   

11.
Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.  相似文献   

12.
The erythrocyte-exchanged chimera mouse model has become to be a significant tool for studying animal and human (hu) protozoan haemoparasites, though the usefulness of this model varies depending primarily on the acceptability of xenogeneic red blood cells (RBC). To find a superior recipient in comparison with C.B-17/Jcl mouse with severe combined immuno-deficiency (scid) mutation, we examined in this report the non-obese diabetes (NOD)/shi-scid mouse, a recently available strain of SCID. When 2.5 x 10(8) of fluorescent dye-labeled hu-RBCs were transfused, C.B-17scid mouse eliminated them logarithmically by a simple linear regression, while NOD-scid mouse eradicated hu-RBCs by a unique two-step fashion, i.e., a potent but only briefly functioning RBC eradication followed by a weak steadily functioning step. The means of regression line constance +/- their standard deviations (SD) of 205 C.B-17scid and of 213 NOD-scid mice for their short- and long-lasting steps were -0.73 +/- 0.63, -0.53 +/- 0.25 and -0.16 +/- 0.10, respectively. Hu-RBC half-lives determined from these means of C.B-17scid mice and of NOD-scid mice for the short- and long-living steps were 3.6, 4.9 and 16.3 hr, respectively. Higher hu-RBC acceptability of NOD-scid mouse, especially at their long-lasting step, was also demonstrated under at an activated state of mouse innate immunity. Treatment with 1.0 mg heat-killed Candida cells caused an acceleration of hu-RBC elimination in both mouse strains but the magnitudes for the short- and long-living steps of NOD-scid mice evaluated by "stimulation index" were only 1/2.6 and 1/7.6 of C.B-17scid mice, respectively.  相似文献   

13.
This study aimed to assess the sex differences in the feeding behaviour of non-obese diabetic severe combined immunodeficient (NOD SCID) mice in a pharmacological model of type 1 diabetes mellitus (T1Dm). In our study, we chose NOD SCID mice of both sexes and assessed their feeding behaviour, body weight, body fat and water content under identical experimental conditions and diets. After 1 month of diabetes mellitus in mice in the experimental group, males and females did not show any increase in body weight, and they weighed significantly less than the control group. However, compared with the control group, in females with a background of T1Dm, there was a significant decrease in body fat. The amount of water consumed in the experimental groups was higher than that in the control groups. The amount of food consumed by males increased when they increased their water consumption, whereas food consumption in females decreased significantly with an increase in water consumption. Thus, we discovered sex differences in the feeding behaviour, body weight and body fat and water content in the pharmacological model of T1Dm after 1 month in NOD SCID mice.  相似文献   

14.
Hypoxic conditions in various cancers are believed to relate with their malignancy, and hypoxia inducible factor-1α (HIF-1α) has been shown to be a major regulator of the response to low oxygen. In this study, we examined HIF-1α expression in canine lymphoma using cell lines and clinical samples and found that these cells expressed HIF-1α. Moreover, the HIF-1α inhibitors, echinomycin, YC-1 and 2-methoxyestradiol, suppressed the proliferation of canine lymphoma cell lines. In a xenograft model using NOD/scid mice, echinomycin treatment resulted in a dose-dependent regression of the tumor. Our results suggest that HIF-1α contributes to the proliferation and/or survival of canine lymphoma cells. Therefore, HIF-1α inhibitors may be potential agents to treat canine lymphoma.  相似文献   

15.
A study was conducted to compare immunogenicity of a Brucella abortus lipopolysaccharide (LPS) and the duration of infection in 5 strains of mice. Mice of strains CBA/NJ, BALB/c, CD-1, C3H/HeN, and C3H/HeJ were allotted into 2 large groups (vaccinated with proteinase K-treated LPS or nonvaccinated) and 6 subgroups based on the intervals between challenge exposure to B abortus strain 2308 and the week the response data were obtained. Criteria used in comparing responses between the various strains of mice as well as between vaccinated and nonvaccinated mice were splenomegaly, colony-forming units (CFU) from spleens, and antibody titers. Responses were evaluated at 1, 2, 3, 5, 8, and 12 weeks after challenge exposure. Results indicated that all strains of mice became infected and maintained infection throughout the 12-week period, the percentages of mice infected were significantly (P less than 0.05) less in vaccinated mice for the first 5 weeks after challenge exposure, and there were no direct correlations between increased immunoglobulins (IgM and IgG titers) and reduction in CFU. Vaccinated mice of strains BALB/c, CD-1, C3H/HeN, and C3H/HeJ had increased titers when challenge exposed and also had significantly (P less than 0.05) smaller spleens and lower CFU. Vaccinated CBA/NJ mice did not have marked antibody titers. The overall results indicated that vaccination with LPS offers some initial protection against B abortus strain 2308 infection, but this protection disappears gradually and in various degrees in the 5 strains of mice studied.  相似文献   

16.
The long term immune responsiveness of bovine peripheral blood lymphocytes engrafted into severe combined immunodeficient mice (bovine PBL SCID mice) was analyzed. After intraperitoneal transfer (i.p.) of 2x10(7) bovine PBL into SCID mice, FACS analysis revealed successful engraftment of bovine CD4 and CD8+ T cells in the peritoneal cavity, the peripheral blood, spleen, lymph nodes, bone marrow, and thymus of reconstituted mice for up to 13 weeks. As shown by immunocytochemistry in sections of spleens from SCID mice 16 weeks after substitution, bovine T and B cells were localized perivasculary forming pseudofollicular structures. Nevertheless, histopathology of spleen and liver from bovine PBL SCID mice revealed pathological alterations indicating rejection of xenogenic cells or graft versus host disease (GVHD). On the functional level, i.p. transfer of bovine PBL into SCID mice induced increasing levels of bovine IgM and IgG in the sera of recipients. Bovine Ig could be detected up to 20 weeks. Immunization of SCID mice reconstituted with PBL of normal donors with dinitrophenol (DNP)-edestin induced a weak specific bovine antibody response in recipient mice. In contrast, a secondary specific bovine IgG response was observed after antigen restimulation of SCID mice reconstituted with PBL from calves preimmunized either with DNP-edestin or keyhole limpet hemocyanin (KLH) showing functional T cell-independent and -dependent antibody responses of bovine PBL SCID mice. Our data demonstrate that transfer of bovine PBL into SCID mice leads to a long term engraftment of bovine cells in lymphatic and non-lymphatic organs inducing a functional substitution of T and B cell immune response of SCID mice. Therefore, bovine PBL SCID chimera can serve as a small animal model for the analysis of bovine lymphopoiesis and infectious diseases of cattle.  相似文献   

17.
NOD1 (Card4) and NOD2 (Card15) are thought to be responsible for cytoplasmic defense against bacterial entry. To gain further knowledge about how their expressions are regulated in murine macrophages, we investigated the expression of NOD1 and NOD2 mRNAs after stimulation with various endotoxins, lipopolysaccharide, lipoteichoic acid and peptidoglycan. In macrophage RAW264.7 cells, the first and second rises in NOD1 and NOD2 mRNAs were observed at 2 hr and at 8-12 hr after endotoxin treatment. Increases in NOD1 and NOD2 mRNAs at 2 hr in lipopolysaccharide-treated RAW264.7 cells were reduced with the use of NF-kappaB inhibitor, caffeic acid phenethyl ester. In RAW264.7 cells, lipopolysaccharide-induced increases in NOD1 and NOD2 mRNAs were inhibited with anti-TLR4 antibody, and partially reduced in peritoneal macrophages obtained from TLR4-deficient mice. Furthermore, NOD1 and NOD2 mRNA expressions in RAW264.7 cells were increased by the treatment with proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), or IL-6. In TNF-alpha deficient macrophages, the expression of NOD molecules was minimal at 12 hr, and the second rise in NOD mRNA seen in lipopolysaccharide-treated RAW264.7 cells was inhibited with anti-TNF-alpha, but not with anti-IL-1beta or anti-IL-6 antibody. These observations suggest that immediate response of NODs to endotoxins could result from NF-kappaB activation via TLR signaling, whereas the second rise in NOD mRNAs might have resulted from TNF-alpha production possibly through NF-kappaB, TLR, and/or NOD signalings.  相似文献   

18.
To study the canine immune system we generated a mouse model engrafted with canine lymphocytes using NOD SCID IL2R common gamma chain ?/? (NSG) mice as recipients (Ca-PBL-SCID). Engraftment of canine peripheral blood lymphocytes (PBLs) was determined post-injection with 107 peripheral blood mononuclear cells (PBMCs) into irradiated NSG mice using flow cytometry and fluorescently labeled antibodies specific to canine helper T cells (CD45+ CD4+), cytotoxic lymphocytes (CD45+ CD8+), regulatory T cells (CD45+ CD4+ Foxp3+), and B cells (CD45+ Ig+ CD21lo). Canine CD45+ lymphocytes were detectable as early as day 1 in the peritoneal cavity, and beginning at 9 days in the blood, bone marrow, and spleen. CD4+ T cells, of which Foxp-3+ CD25hi cells constituted a minor percentage, were the predominant lymphocyte population at 9 days post engraftment contrasting with increasing proportions of CD8+ CTL's and Ig+ B cells beginning at 16 days. Canine immunoglobulin was initially detected in the serum of Ca-PBL-SCID mice at 9 days post-engraftment and peaked in concentration at day 36. From day 28 to 52 post-engraftment 30% of the Ca-PBL-SCID mice became markedly anemic and thrombocytopenic, yet gross and histopathologic examination of bone marrow, kidneys, spleen, liver, and intestine revealed no obvious lesions. Blood smear evaluation revealed agglutination of mature red blood cells, reticulocytes and a regenerative anemia. These findings demonstrate that NSG mice are capable of engraftment of canine PBLs yet develop graft versus host disease similar to Hu-PBL-SCID mice.  相似文献   

19.
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20.
To compare and summarize the mechanisms, frequencies of occurrence, and classification schemes of spontaneous, experimental, and genetically engineered mouse skeletal neoplasms, the literature was reviewed, and archived case material at The Jackson Laboratory was examined. The frequency of occurrence of spontaneous bone neoplasms was less than 1% for most strains, with the exceptions of osteomas in CF-1 (5.5% and 10% in two studies) and OF-1 outbred strains (35%), and osteosarcomas in NOD/ShiLtJ (11.5%) and NOD-derived (7.1%) mice. The frequency was 100% for osteochondromas induced by conditional inactivation of exostoses (multiple) 1 (Ext1) in chondrocytes, osteosarcomas induced by tibial intramedullary inoculation of Moloney murine sarcoma virus, and osteosarcomas induced by conditional inactivation of Trp53-with or without inactivation of Rb1-in osteoblast precursors. Spontaneous osteogenic neoplasms were more frequent than spontaneous cartilaginous and vascular types. Malignant neoplasms were more frequent than benign ones. The age of occurrence for spontaneous neoplasms ranged from 37 to 720 days (M = 316.35) for benign neoplasms and 35 to 990 (M = 299.28) days for malignant. In genetically engineered mice, the average age of occurrence ranged from 28 to 70 days for benign and from 35 to 690 days for malignant. Histologically, nonosteogenic neoplasms were similar across strains and mutant stocks; osteogenic neoplasms exhibited greater diversity. This comparison and summarization of mouse bone neoplasms provides valuable information for the selection of strains to create, compare, and validate models of bone neoplasms.  相似文献   

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