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1.
Adult severe combined immunodeficient (SCID) mice were inoculated with oocysts of 13 different Caryospora (Protozoa, Apicomplexa) species isolated from the faeces of 10 reptilian and three raptorial bird hosts in attempt to test heteroxenous life cycle pattern. Only three reptilian isolates originated from viperid snakes, namely from Calloselasma rhodostoma, Atheris nitschei and Vipera ursinii induced lethal dermal caryosporosis in SCID mice. Neither clinical signs nor developmental stages were observed in mice infected with further nine caryosporan isolates originated from other reptilian and raptorial bird hosts. Results of this study confirmed that SCID mice represent a useful tool for evaluation of heteroxenous life cycle pattern of caryosporan coccidia and that only the Caryospora species from viperid and crotalid snakes produce dermal caryosporosis in mice  相似文献   

2.
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   

3.
Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient horses. To address this question we adoptively transferred EIAV Rev-specific CTL clones into four EIAV-challenged SCID foals, concurrent with low-dose aldesleukin (180,000U/m2), a modified recombinant human IL-2 (rhuIL-2) product. The dose was calculated based on the specific activity on equine PBMC in vitro, and resulted in plasma concentrations considered sufficient to saturate high affinity IL-2 receptors in humans. Despite specific activity on equine PBMC that was equivalent to recombinant equine IL-2 and another form of rhuIL-2, aldesleukin did not support the engraftment and expansion of infused CTL clones, and control of viral load and clinical disease did not occur. It was concluded that survival of Rev-specific CTL clones infused into EIAV-challenged SCID foals was not enhanced by aldesleukin at the doses used in this study, and that in vitro specific activity did not correlate with in vivo efficacy. Successful adoptive immunotherapy with CTL clones in immunodeficient horses will likely require higher doses of rhuIL-2, co-infusion of CD4+ T lymphocytes, or administration of equine IL-2.  相似文献   

4.

Background

The carrier status of lavender foal syndrome (LFS), cerebellar abiotrophy (CA), severe combined immunodeficiency (SCID), and occipitoatlantoaxial malformation (OAAM1) in foals with juvenile idiopathic epilepsy (JIE) is unknown.

Hypothesis/Objectives

To determine the carrier status of LFS, CA, SCID, and OAAM1 in foals with JIE.

Animals

Ten foals with JIE.

Materials and Methods

Archived DNA samples were tested for known genetic mutations causing LFS, CA, SCID, and OAAM1. The inclusion criteria consisted of having been diagnosed with JIE by ruling out other causes of seizures in foals and supported by electroencephalographic examination.

Results

Ten Egyptian Arabian horses (5 females and 5 males) were phenotyped as foals with JIE by electroencephalography (EEG). All foals were negative for the genetic mutations that cause LFS, CA, SCID, and OAAM1 except for 1 foal that was a carrier of CA.

Conclusions and Clinical Importance

Juvenile idiopathic epilepsy of Egyptian Arabian foals and LFS appear to be phenotypically and genetically distinct disorders. There was no apparent association between JIE and LFS, CA, SCID, and OAAM1.  相似文献   

5.
The effectiveness of Doxil as a new chemotherapeutic agent against canine transmissible venereal tumor was evaluated, using NOD/ SCID and CD1-nu xenograft mouse models and the response between the two mouse strains was compared. Samples of xenografted venereal tumor were inoculated SC into 20 six week-old NOD/SCID mice and 20 six week-old CD1-nu mice. Seven weeks later, tumor-bearing mice were divided into treatment and control groups. Treatment group was injected with Doxil (6 mg/kg, IP, as a single injection). Control group was injected with buffered saline (0.75cc, IP). Tumor size was determined by caliper measurements and tumor response was assessed according to standard criteria. In both strains there was a significant decrease in tumor size in response to Doxil treatment (P<0.0001). In CD1-nu eight out of nine tumors (88%) responded to the treatment, and in 2 cases complete remission was observed. In NOD/SCID group response to the treatment was seen in eight out of ten tumors (80%) but none regressed fully. Response to the treatment was statistically equal in both strains even though the apoptotic rate, confirmed by TUNEL staining, was higher in NOD/SCID than in CD-1-nu (8.65% and 0.7%, respectively) and tumor infiltrating cells were different: eosinophils in NOD/SCID and CD45R-positive B lymphocytes, and plasma cells in CD-1-nu. In untreated CD1-nu mice, tumor progress was slower than in NOD/SCID. Our results indicate that Doxil is effective against CTVT in mouse xenograft models.  相似文献   

6.
To determine whether functional T- and B-cells can affect differentiation and/or proliferation of uterine natural killer (uNK) cells, their numbers in SCID mice (genotype, C.B.-17/Icr-scid/scid) were compared with those of control mice (genotype, C.B.-17/Icr-+/+) on days 8, 12 and 16 of pregnancy. Using biotinylated-Dolichos biflorus agglutinin (DBA) lectin staining, uNK cells can be readily classified into 4 subtypes, I to IV, from immature to mature types. The number of uNK cells was significantly lower in the decidua basalis of SCID mice than in that of control mice on day 8 of pregnancy. Particularly, the number of uNK cells of immature subtype II was significantly lower in SCID mice than in the control mice. By day 12, however, the uNK cell number in the SCID mice reached the same level as that of the control mice. It is likely that uNK cell differentiation in SCID mice was delayed during the early placentation period due to a lack of functional T and B cells.  相似文献   

7.
Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring among Arabian or crossbred Arabian horses. The genetic defect responsible was previously identified as a 5‐base pair deletion in the gene encoding the catalytic subunit of the DNA dependant protein kinase (DNA‐PKcs). This study was carried out to determine the frequency of SCID and identify horses carrying the gene for SCID among Arabian and Arabian crossbred stallions and mares in Morocco using a DNA‐based test. Twenty‐one horses were SCID carriers: 14 (7%) Arabians, 6 (4%) Arab‐Barbs and one (3.3%) Anglo‐Arab. After analysing their genealogy, 3 imported stallions were identified that disseminated the mutant gene of DNA‐PKcs in Morocco.  相似文献   

8.
本研究对ＳＣＩＤ小鼠与ＢＡＬＢ／ｃ小鼠的阴道开口时间,卵泡发育,精子发生及血浆促黄体素（ＬＨ）和睾酮（Ｔ）浓度进行了比较观察,结果表明,２种鼠阴道开口时间均为４０日龄,均在３０日龄时卵巢出现有腔卵泡,但ＳＣＩＤ雌鼠４５日龄有排卵,而同龄ＢＡＬＢ／ｃ雌鼠未见排卵;ＳＣＩＤ雄鼠４０日龄附睾涂片有活精子,ＢＡＬＢ／ｃ雄鼠４５日龄附睾涂片可见活精子,ＳＣＩＤ小鼠初情期似乎有比ＢＡＬＢ／ｃ小鼠初情期略早的趋  相似文献   

9.
Clearance of Theileria sergenti-infected bovine red blood cells (Bo-RBCs) from the blood circulation of severe combined immune deficiency (SCID) mice was studied to help understand the mechanisms of anemia developing in cattle infected with T. sergenti. For the clearance test, Bo-RBC samples having 2%, 58%, and 76% parasitemia and, as a control, parasite-free Bo-RBCs were prepared in the Bo-RBC-SCID mouse model. The T. sergenti-infected Bo-RBCs and the uninfected control Bo-RBCs were separately labeled with two, green and red, fluorescent dyes, mixed together, and injected intravenously into SCID mice. The blood samples collected at various time points were observed under a fluorescent microscope, and the numbers of green and red fluorescing RBCs were counted differentially to determine the clearance rates of T. sergenti-infected and uninfected Bo-RBCs. This test clearly demonstrated that the Bo-RBC samples having higher parasitemias were cleared faster from the blood circulation of SCID mice. The results suggest that the intravascular clearance system in SCID mice may have a mechanism by which T. sergenti-parasitized and non-parasitized Bo-RBCs are recognized and cleared differentially.  相似文献   

10.
We isolated Cryptosporidium parvum-type oocysts from naturally infected siberian chipmunks which originated in the People's Republic of China and examined the infectivity to rodents as experimental animals. The naturally infected chipmunks did not show any clinical symptoms. The oocysts were 4.8 x 4.2 microm on average in size. They were ovoid and morphologically similar to the C. parvum oocysts isolated from human and cattle. Experimental rodents were inoculated with 1.6 x 10(6) original oocysts each. SCID mice began to shed oocysts on day 7 and the OPG value was 10(5) from 50 days. The oocysts were found from ICR mice on days 13 and 16 by only sugar flotation method, however, any oocysts were not detected from the rats, guinea pigs and rabbits until 30 days. Two infected SCID mice were necropsied on days 100 and 102 and examined for coccidian organisms. Merozoites and oocysts were found in the low part of jejunum and ileum, however, no parasites were detected in the stomach. Consequently, it was considered that the present species was C. parvum and was probably genotype 2 from result of infectivity to rodents.  相似文献   

11.
To investigate the pathogenesis of respiratory lesions caused by the facultative intracellular pathogen, Rhodococcus equi, pulmonary clearance was compared in four groups of genetically defined mice, chosen for their specific deficits in immune and inflammatory responses. Complement-deficient A/J, immunodeficient nu/nu (nude), scid/scid.bg/bg (SCID/beige), C57BI/6J.bg/bg (beige) and normal Swiss mice (SW) received approximately 10(7) R. equi intranasally on day 0. Bacterial clearance was assessed in lung, liver and spleen on days 1, 4, 7 and 14. Pulmonary clearance was not significantly different between SW and A/J mice. Beige mice cleared R. equi more rapidly and completely than A/J and SW, indicating that deficits in phagocytic and NK cell function associated with the bg/bg gene did not compromise clearance. Pulmonary clearance in immunodeficient SCID/beige mice paralleled that of the SW and A/J mice initially but bacterial proliferation produced significant differences from SW mice at day 14. Nude mice were unable to clear R. equi from day 1, resulting in the death of two nude mice at day 11. Both SCID/beige and nude mice developed severe pyogranulomatous bronchopneumonia, whereas A/J and SW mice developed transient pulmonary lesions. Beige mice developed minimal lung lesions. Significant systemic bacterial proliferation occurred only in nude and SCID/beige mice. We conclude that deficiencies in complement components, phagocytic and NK cells do not impair the pulmonary clearance of R. equi but that a competent cellular immune system is required to prevent pneumonia and death. The difference in early phase pulmonary clearance in nude and SCID/beige mice indicates two phases are important for clearance. An acapsular mutant of R. equi was completely cleared from the lungs of SCID/beige mice suggesting an important role for the capsule in virulence for mice.  相似文献   

12.
Severe combined immunodeficiency disease (SCID) in foals is the only known animal model for the autosomal recessive form of primary SCID in man. A major requirement in the treatment of SCID is the maintenance of the patient in a disease free state until definitive therapy can be undertaken. This paper reviews the current status of prophylactic and definitive therapy in man and the horse. Particular emphasis is placed on the methods of reconstitution available, involving foetal tissues and bone marrow.  相似文献   

13.
The viability and infectivity of Cryptosporidium parvum (C. parvum) oocysts, detected in water samples collected from river water in Hokkaido, were investigated using Severe Combined Immunodeficient (SCID) mice. The water samples collected from September 27 through October 10, 2001 by filtration using Cuno cartridge filters were purified and concentrated by the discontinuous centrifugal flotation method. From 1.2 x 10 (5) liters of the raw river water, approximately 2 x 10(4) oocysts were obtained and designated as Hokkaido river water 1 isolate (HRW-1). Oocyst identification was carried out using microscopic and immunological methods. Six 8-week-old female SCID mice were each inoculated orally with 1 x 10 (3) oocysts. Infection was successfully induced, resulting in fecal oocyst shedding. Oocysts were then maintained by sub-inoculation into SCID mice every 3 months. Infectivity was evaluated by making comparisons with two known C. parvum stocks, HNJ-1 and TK-1, which were bovine genotypes detected in fecal samples from a cryptosporidiosis patient and young cattle raised in Tokachi, Hokkaido respectively. The oocyst genotypes were determined from a small subunit ribosomal RNA (SSU-rRNA) gene by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis. No significant differences were observed in the average number of oocysts per gram of feces (OPG) in any of the isolates. Our data indicates that the C. parvum oocysts detected in the sampled river water were of C. parvum genotype 2. Moreover, our data on the continued isolation, detection and identification of the C. parvum isolates is consistent with the available epidemiological data for the Tokachi area.  相似文献   

14.
The effectiveness of 6 antitumor agents has been evaluated for canine mammary gland tumor (CMG-6) serially transplanted into severe combined immunodeficiency (SCID) mice. CMG-6 diagnosed as a solid carcinoma was subcutaneously transplanted into SCID mice and six antitumor agents were intravenously given to the mice as a single injection. The effectiveness was evaluated by Treatment group/Control group percent (T/C %) and statistical significance determined by Mann-Whitney's U-test in tumor volume. The minimum effective doses (MEDs; mg/kg) of mice were as follows; cyclophosphamide (CPM) 65, doxorubicin (DXR) 6, cisplatin (CDDP) 5, vincristine (VCR) 1.6, vinblastine (VLB) more than 5.5, 5-fluorouracil (5-FU) 105. Clinical effects of the drugs were predicted based on area under the curve (AUC) of dogs given a clinical dose (AUCdog)/AUC of mice given a MED (AUCmouse) ratios from published references. The AUC ratios were as follows; CPM 2.24, DXR 0.19, CDDP 1.20, VCR 0.04, VLB <1.24 and 5-FU 1.15. Drugs indicating more than 1.0 in AUCdog/AUCmouse ratio were CPM, CDDP and 5-FU, and would be suggested as effective in the original patient with CMG-6. The combination chemotherapy using clinically equivalent doses in CDDP and CPM, which were the two highest values in AUCdog/AUCmouse ratio by single agent therapy, was performed and shown to have additional effects as compared to the responsiveness of each agent against CMG-6.  相似文献   

15.
Severe combined immunodeficiency (SCID) is an inherited disorder of humans, mice, horses, and dogs, in which affected individuals are incapable of generating antigen-specific immune responses. It occurs when lymphocyte precursors fail to differentiate into mature lymphocytes because of mutations within recombinase-activating genes 1 and 2 or within the genes encoding deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK). It also occurs when differentiated lymphocytes are incapable of completing signal transduction pathways because of defects in cell surface receptors for interleukins (IL). A spontaneous mutation in DNA-PKcs of BALB/c mice results in SCID, as do experimentally induced mutations in RAG1 and RAG2. SCID in horses results from a spontaneous mutation in DNA-PKcs. Two molecular mechanisms account for SCID in dogs. Jack Russell Terriers have a mutation within the DNA-PKcs gene, whereas Cardigan Welsh Corgi and Basset Hound have different defects in the gene encoding the gamma chain that is common to the receptors for IL-2, -4, -7, -9, -15, and -21. The location of the mutation within target genes influences the spectrum of diseases observed in affected animals.  相似文献   

16.
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   

17.
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   

18.
To develop a model of bovine thymus and lymph node growth in vivo, we have implanted bovine foetal tissues (16-23 weeks gestation) under the renal capsule of severe combined immune deficient (SCID)/beige (BG) mice and assayed for graft growth and characteristics 2-18 weeks after engraftment. Bovine foetal thymus and lymph node grew considerably following engraftment of SCID/BG mice. Growth was optimal if bovine foetal tissues were used before gestation Week 17. Bovine-mouse chimerism was confirmed using glucose phosphate isomerase analysis. Bovine thymus grew during the entire 18 weeks of study. Growth of bovine lymph node was initially rapid, reaching a maximum at 2 weeks after transplantation followed by a progressive decrease in size. Transplanted bovine lymph node and thymus were morphologically similar to age-matched bovine foetal tissue for a limited time period. Fibrosis, degeneration and depletion of lymphocytes were evident 6 weeks after engraftment; changes were more severe in lymph node than in thymus whereas increases in lymphocytes, lymphopoiesis and follicle formation were evident in age-matched bovine foetal tissue. Despite growth and morphological similarities of the transplanted tissue, blood counts suggested there was no peripheralization of bovine leucocytes. Bovine immunoglobulins (IgG1 and IgG2) were detected in serum of some SCID/BG chimeric mice for a limited time. The appearance of bovine immunoglobulins at 2 weeks in SCID/BG chimeric mice depended on the age of the foetal donor (> 18 weeks) and coincided with the appearance of morphologically mature lymphocytes in the donor foetus lymph nodes. The ability to produce bovine immunoglobulins decreased 8 weeks after engraftment, coinciding with the depletion of lymphocytes in the engrafted lymph node. Lymphocyte depletion and loss of function of engrafted tissues appear the result of a lack of lymphoid progenitors normally derived from hematopoietic stem cells in the bone marrow.  相似文献   

19.
Chemoradiotherapy in young women with cancer has substantially improved life expectancy in these patients, but these treatments often cause infertility. One method of preserving fertility is to cryopreserve ovarian tissue. In this study, an automatic open-vessel freezing system with self-seeding was tested for cryopreservation of murine ovarian tissue; the mouse is a species widely used in human and veterinary medical research. The freezing system concerned, is used for cryopreservation of oocytes and embryos in Europe. Twenty severe combined immunodeficiency (SCID) mice were ovariectomized. The ovarian tissue was either directly transplanted heterotopically into the neck muscle (group 1, n = 6) or cryopreserved after equilibration with 1.5 M dimethylsulphoxide and propanediol. After thawing, the tissue was transplanted in SCID mice (group 2, n = 6). Before and after thawing, a part of the ovarian tissue was examined with the LIVE/DEAD fluorescent viability staining. The count of follicles revealed intact (fresh 24.1%/thawed 21.7%), impaired (fresh 35.1%/thawed 35.4%), and dead follicles (fresh 40.8%/thawed 42.9%). The healthy follicular loss because of the cryopreservation was 10.0%. All recipient mice were killed after 3 weeks. Transplanted ovarian tissue was found macroscopically in all mice. Histological examination showed several growing follicles in all developmental phases in both groups of SCID mice [group 1 (fresh grafts): 315 +/- 76.3 (mean +/- SD); group 2 (cryopreserved grafts): 237 +/- 63.4]. These results demonstrate that the use of an open-freezing system allows the survival of cryopreserved mouse ovarian tissue.  相似文献   

20.
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   

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