SEARCH · PubMed Health

Results for “SCID mouse”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2004

Involvement of telomere dysfunction in the induction of genomic instability by radiation in scid mouse cells.

To determine the effects of a defect in NHEJ on the induction of genomic instability by radiation, we investigated X-ray-induced delayed chromosomal aberrations such as dicentrics and fragments in scid mouse cells. We found that radiosensitive scid mouse cells are more susceptible than wild-type mouse cells to the induction of delayed chromosomal aberrations when the cells are exposed to an equivalent survival dose of X-rays. Telomere FISH analysis revealed that radiation enhances the induction of telomeric fusions where telomeric sequences remain at the fused position (tel+ end-fusions), suggesting that radiation induces telomere dysfunction. Moreover, formation of the tel+ end-fusions was found to be enhanced in scid mouse cells, suggesting that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a role in telomeric stabilization. Thus, the present study suggests that a cause of genomic instability is telomere dysfunction induced by radiation and that a defect in DNA-PKcs enhances the telomeric destabilization.

Animals↗

PubMed1993

Propagation of human papillomavirus type 11 in human xenografts using the severe combined immunodeficiency (SCID) mouse and comparison to the nude mouse model.

We report propagation of human papillomavirus (HPV) type 11 in human xenografts in the severe combined immunodeficiency (SCID) mouse and compare this new animal model for HPV infection to the previously established athymic nude mouse model. HPV-11-infected foreskin fragments grafted under the renal capsule of SCID mice formed large epithelial cysts that had the histologic and immunocytochemical features of HPV infection. This infection was successfully passaged to nude mice. Viral particles that reacted to an antibody directed to HPV-11 virions were identified from samples recovered from the SCID and nude mice. Viral DNA sequence analysis confirmed that the passaged virus was HPV-11. In a comparative experiment of the nude mouse and SCID mouse models, the latter produced HPV-11-infected xenografts that were larger and more often positive for HPV by immunocytochemistry and presence of viral mRNA than those propagated in the former model. Finally, we observed that growth of HPV-11-infected foreskin fragments in the SCID mouse model is not restricted to the kidney as in the nude mouse, but also can occur in the subcutis and the peritoneum.

Animals↗

PubMed1994

SCID mouse spleen does not support scrapie agent replication.

BALB/c and severe combined immunodeficiency (SCID) mice were inoculated intracerebrally or intraperitoneally with scrapie agent strain ME7 to examine the role of functional lymphocytes and follicular dendritic cells in splenic infectivity and PrPSc accumulation. Intracerebrally inoculated BALB/c and SCID mice developed the clinical signs and microscopic lesions characteristic of scrapie. Spleens from terminally affected BALB/c mice contained PrPSc which was detectable by immunoblot analysis; SCID mouse spleens did not contain detectable PrPSc. SCID mouse spleens collected during the first 90 days after intraperitoneal infection contained neither infectivity nor PrPSc.

Amino Acid Sequence↗

PubMed2002

Radiation-induced apoptosis in the scid mouse spleen after low dose-rate irradiation.

PURPOSE: To elucidate the process of radioadaptation, the role of DNA-PK activity was examined using the scid mouse defective in DNA-PKcs. MATERIALS AND METHODS: The induction of apoptosis in the spleens of the C.B-17 Icr scid mouse and the parental mouse was studied after chronic irradiation with gamma-rays at 1.5 Gy (0.001 Gy min(-1) for 25 h) followed by challenge irradiation with X-rays at 3.0 Gy (1.0 Gy min(-1) for 3 min). RESULTS: When the wild-type mouse was previously exposed to chronic irradiation (1.5 Gy) at a low dose-rate (0.001 Gy min(-1)), apoptosis induced by acute irradiation (3.0 Gy, 1.0 Gy min(-1)) was significantly suppressed, especially in the splenic white pulp. There was no change by acute irradiation after chronic irradiation in the scid mouse, although an effect was detected in the spleen after acute irradiation alone. CONCLUSIONS: These data suggest that DNA-PK activity might play a major role in the radioadaptive response following pre-irradiation at a low dose-rate.

Animals↗

PubMed1995

Thermal response and hyperthermic radiosensitization of scid mouse bone marrow CFU-C.

PURPOSE: Scid mice are severely immunodeficient as a result of a defective recombinase system. Mice with the scid mutation have been shown to have an increased sensitivity to ionizing radiation, presumably as a result of an inability to repair DNA damage. Little is known of the impact of this mutation on the thermal response and on hyperthermic radiosensitization. This investigation established the thermal response (42-44 degrees C), patterns of thermotolerance development, and the impact of hyperthermia (60 min at 40 degrees C or 42 degrees C) on the radiation response of bone marrow colony forming unit-culture cells (CFU-C) in scid mice. METHODS AND MATERIALS: Anesthetized scid mice (pentobarbital, 90 mg/kg) were killed by cervical dislocation and the nucleated marrow obtained from both tibia and femora by passing 2 ml of cold McCoy's 5A medium supplemented with 15% fetal bovine serum through each bone. Single cell suspensions of nucleated marrow were heated in 12 x 75 mm sterile tissue culture tubes at a concentration of approximately 5 x 10(6) cells/ml. Radiation, when used, was delivered immediately prior to hyperthermia by a 137Cs irradiator (dose rate of 1.20 Gy/min). Colony forming unit-culture were cultured in semisolid agar in the presence of colony stimulating factor (conditioned medium from L929 cells) for 7 days. RESULTS: The slope of the radiation dose-response curve for CFU-C in scid mice was biphasic, the Dos (+/- SE) were 0.29 +/- 0.03 Gy and 1.09 +/- 0.20 Gy, respectively. The Dos of the radiation dose-response curve for wild type marrow from CB-17 and Balb/c mice were 1.28 +/- 0.05 Gy and 1.47 +/- 0.15 Gy, respectively. The Dos of the hyperthermia dose-response curves for scid mice were 75 +/- 5, 10 +/- 1.4, and 4 +/- 0.2 min, respectively, for temperatures of 42 degrees, 43 degrees, and 44 degrees C. Thermotolerance development at 37 degrees C increased to a maximum at approximately 240 min after acute hyperthermia (15 min at 44 degrees C) and thereafter, decreased to control levels within 15 h. Thermotolerance did not develop in scid CFU-C during chronic hyperthermia at temperatures < 42.5 degrees C. Hyperthermia (60 min at 40 degrees or 42 degrees C) immediately after ionizing radiation did not significantly alter the terminal slope of the radiation dose-response curve of scid CFU-C (Do = 1.28 +/- 0.08 Gy). By contrast, hyperthermia following radiation of wild type CFU-C resulted in a decrease in the Do from 1.47 +/- 0.05 Gy (Balb/c, rad only) to 1.31 +/- 0.08 or 1.06 +/- 0.18 Gy for 60 min at 40 degrees or 42 degrees C, respectively. CONCLUSION: These results show that the thermal response and the pattern of thermotolerance development of scid CFU-C were similar to that of wild type Balb/c CFU-C, but that hyperthermia given immediately after ionizing radiation did not alter the radiation response of scid CFU-C. The scid mutation does not increase hyperthermic sensitivity or change the pattern of thermotolerance development of scid mouse CFU-C, implying that the scid mutation is not involved with thermal response, but does render the already radiation-sensitive scid cells incapable of thermal radiosensitization.

Animals↗

PubMed2000

Tumorigenesis of Epstein-Barr virus-positive epithelial cell lines derived from gastric tissues in the SCID mouse.

To study the tumorigenesis of Epstein-Barr virus (EBV)-positive epithelial cell lines GT38 and GT39 derived from human gastric tissues, we inoculated these cells under the skin of severe combined immunodeficient (SCID) mice. The development of tumors was observed in each of the mice about 2 months after the inoculation. The tumors were diagnosed with undifferentiated carcinoma by hematoxylin/eosin staining. EBV-encoded small RNA1 was detected in the paraffin-embedded tumor sections. The tumor cells had human chromosome. The circular, but not linear, EBV DNA was detected in the tumors. The molecular sizes of EBV DNA termini were the same as that of the inoculated GT38 or GT39 cells. The expressions of EBV nuclear antigen 2 and latent membrane protein 1 reduced in the tumors. Transcripts of BamHI C and W promoters in latency III were detected in the tumors and the cultured cells in vitro. The tumor cells were passaged from one SCID mouse to other SCID mice and to cultures in vitro. This is the first evidence that the EBV-positive epithelial cell lines produced tumors in the SCID mouse.

Animals↗

PubMed1999

Gene transfer of cytokine inhibitors into human synovial fibroblasts in the SCID mouse model.

OBJECTIVE: To investigate the effects of retrovirus-based gene delivery of inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in the SCID mouse model of rheumatoid arthritis (RA). METHODS: The MFG vector was used for gene delivery of tumor necrosis factor alpha receptor (TNFalphaR) p55, viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The effect on invasion of these cells into human articular cartilage and on perichondrocytic cartilage degradation was examined after 60 days of coimplantation into the SCID mouse. RESULTS: TNFalphaR p55 gene transfer showed only a limited effect on inhibition of RA synovial fibroblast invasiveness and cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into the coimplanted cartilage was strongly inhibited by both viral and murine IL-10. Perichondrocytic cartilage degradation was not affected by either form of IL-10. CONCLUSION: The data show that cytokines can be successfully inserted into the genome of human RA synovial fibroblasts using a retroviral vector delivery system, and that the SCID mouse model of human RA is a valuable tool for examining the effects of gene transfer. In addition, inhibition of more than one cytokine pathway may be required to inhibit both synovial- and chondrocyte-mediated cartilage destruction in RA.

Animals↗

PubMed1999

Evaluation of temozolomide in a SCID mouse model of human B-cell precursor leukemia.

We used a SCID mouse model of human B-lineage acute lymphoblastic leukemia to examine the antileukemic activity of temozolomide in comparison to as well as in combination with B43-PAP anti-CD19 immunotoxin. One hundred percent of the 20 PBS-treated control mice died of disseminated human B-lineage ALL at 32 to 64 days after the inoculation of 1x10(6) NALM-6 cells, with a median event free survival time of 43 +/- 1 days. Temozolomide, when administered i.p. for 5 consecutive days at a dose level of 411 mg/m2 or as a single 750 mg/m2 bolus dose, elicited significant antileukemic activity and improved survival in this SCID mouse model of human B-lineage ALL. The median survival times were 43 +/- 1 days for PBS-treated mice, 56 +/- 16 days for mice injected with the 5-day temozolomide program, and 64 +/- 15 days for mice treated with a single bolus dose of temozolomide. However, temozolomide was not as effective as B43-PAP. Whereas only 40 +/- 21% of mice treated with temozolomide survived beyond 120 days, B43-PAP treatment resulted in 74 +/- 7% survival in the same model system. The combination of temozolomide with B43-PAP was well tolerated by mice but it was not significantly more effective than B43-PAP alone. Temozolomide may have very limited potential as an antileukemic agent for treatment of B-lineage ALL.

Animals↗

PubMed1996

SCID mouse as a model for transplantation studies.

Mice expressing the severe combined immunodeficiency trait (SCID) lack functional T and B lymphocytes and have been widely used for the study of B- cell development and for cancer and HIV research. The purpose of this study was to evaluate the SCID mouse as a potential model for T-cell maturation and transplantation studies. C3H/HEN SCID mice screened by fluorescence-activated cell sorting (FACS) and radial immunodiffusion assay (RID) were verified homozygous recessive if CD3-, CD22-, and serum (IgG) <5 mg/liter. C3H/HEN SCID mice pretreated with 250 R total-body gamma irradiation were reconstituted with 2.5 to 4 x 10(7) donor bone marrow cells derived from [syngeneic (syn): male wild-type C3H/HEN, allogeneic (allo): male BALB/c or C57BL/6) mice by intravenous injection. Four weeks post-transplant, engraftment was determined by FACS; repopulation of blood, thymus, and spleen; RID; and histologic evaluation. Immune function against donor, recipient, and third-party antigen was assayed in vitro by mixed lymphocyte response (MLR) and in vivo by full-thickness skin grafting. Greater than 90% of both syngeneic and allogeneic reconstitutions expressed CD3+, CD4+, CD8+, and CD22+ cells of donor origin in peripheral blood and spleen. FACS analyses of lymphocyte subpopulations in blood and spleen were not significantly different between reconstituted SCID mice and wild-type C3H/HEN or BALB/c controls, with engraftment stable for >4 months. No evidence of graft-versus-host disease was observed in stable, long-term (>4 months postreconstitution) chimeras. White blood cell, total thymocyte, and total splenocyte counts were significantly elevated (P < 0.05: ANOVA, Student's t) following reconstitution of homozygous SCID mice to levels found in wild-type controls. Serum (IgG) for reconstituted allo- and syn-SCID mice was consistently > 150 mg/liter (n = 22), with histologic lymphocyte engraftment of spleen, duodenum, and thymus. Histologic examination of lymphocyte engraftment in spleen, duodenum, and thymus was indistinguishable from normal controls in SCID mice after reconstitution. Prior to reconstitution, scant lymphoid cells were observed at these sites. Allo-SCID splenocyte response against third-party antigen was significantly elevated (P < 0.01: ANOVA, Student's t) when compared with donor and recipient antigen response with a proliferation index (PI) comparable to wild-type controls. Unreconstituted SCID mice were unresponsive. In vivo, allo-SCID mice demonstrated rejection of only third-party skin grafts between postoperative days 9 and 14 (controls: postoperative days 7 and 11). The SCID mouse model demonstrates in vitro and in vivo B- and T-cell immune function comparable to that of wild-type mice and provides a useful model for T-cell maturation and transplantation studies.

Animals↗

PubMed1993

Analysis of early reconstitution events in the SCID mouse thymus following rat bone marrow cell transplantation.

In this work, we provide comprehensive evidence that sublethally irradiated Thy-1.2 SCID mice can be used as a model system for thymus homing and reconstitution after intravenous transfer of rat bone marrow cells. Full short-term SCID mouse thymus reconstitutions were obtained using a plastic nonadherent low-density rat bone marrow cell subset. Cell counts and flow cytometric analysis showed that at 3 weeks post-transfer the SCID mouse thymus contained up to 41 x 10(6) Thy-1.1high rat lymphoid cells comprising the expected percentages and distribution of CD2+, CD5+, CD3+, alpha beta TCR+ and CD4+ CD8+ cells. As seen on cryostat sections, bone marrow-derived MHC class II+ accessory cells had already developed by 2 weeks post-transfer, preceding the thymocyte expansion apparent at 3 weeks. Thus, analysis of the early events of SCID thymus reconstitution by rat bone marrow cells shows that they closely resemble those described in congenic animals and points out the temporally distinct development of dendritic cells and thymocytes. The SCID mouse-rat chimera model system represents a new in vivo tool for manipulating rat T-cell differentiation from bone marrow-resident precursor cells and in addition supports our previous xenogeneic reconstitution studies performed in organ culture.

Animals↗

PubMed1991

The SCID mouse.

Numerous investigations of the mammalian hematopoietic system in normal and pathologic states have been facilitated by the study of genetically determined immunologic dysfunctions in experimental animals. This article focuses on the scid mutation of the mouse (SCID mouse) that causes severe defects in the development of the immune system. The mutation appears to impair the recombination of antigen receptor genes, causing in the SCID mice a lack of functional T and B lymphocytes. Other hematopoietic cell types appear to develop and function normally. SCID mice readily support normal lymphocyte differentiation and can be reconstituted with normal lymphocytes from syngeneic or allogeneic mice and even partially reconstituted with human lymphocytes. They also support the growth of allogeneic and xenogeneic tumors. Thus, SCID mice might be useful for studies of both normal and abnormal lymphocyte development and function.

Animals↗

PubMed2004

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: deficits in cognitive function.

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features.

AIDS Dementia Complex↗

PubMed1994

Protective reconstitution of the SCID mouse against reactivation of toxoplasmic encephalitis.

A SCID mouse model of toxoplasmic encephalitis (TE) is described. Immunologic reconstitution using splenocytes from Toxoplasma gondii-immune allogeneic or nonimmune syngeneic donors was not successful in preventing reactivation of TE in chronically infected SCID mice. Splenocytes from immune syngeneic donors successfully prevented reactivation. Flow cytometry of spleens of transplanted mice demonstrated only transient reconstitution with allogeneic cells, but syngeneic lymphocytes exhibited prolonged engraftment. Reconstitution with syngeneic cells allowed enhanced production of T. gondii-specific antibody. In vitro depletion of CD4+ and CD8+ lymphocytes from BALB/c splenocytes before transplantation into infected SCID mice resulted in survival inferior to that of fully reconstituted SCID mice. Depletion of CD4+ or CD8+ cells before transplantation did not result in mortality, but transfer of CD(4+)-depleted splenocytes resulted in histologic evidence of reactivation of TE, whereas transfer of CD(8+)-depleted cells did not. This model could be used for study of the pathogenesis of TE and applied to the evaluation of therapies for TE in immunocompromised hosts.

Animals↗

PubMed2000

Islet xenograft destruction in the hu-PBL-severe combined immunodeficient (SCID) mouse necessitates anti-CD3 preactivation of human immune cells.

Introduction of the hu-PBL-SCID mouse model has yielded a potentially useful tool for research in transplantation. The aim of this study was to define the conditions necessary for a reconstituted human immune system to destroy in a consistent manner rat islet xenografts in the alloxan-diabetic hu-PBL-SCID mouse. We examined different time points of hu-PBL reconstitution, different transplantation sites of the islets and several hu-PBL reconstitution protocols. Major differences in graft destruction were observed between the different hu-PBL reconstitution protocols, irrespective of timing of hu-PBL reconstitution or site of transplantation. Although preactivation of hu-PBL did not improve the level of hu-PBL chimerism, histological and immunohistochemical analysis of the grafts revealed a severe human lymphocytic infiltration and beta cell destruction only in the grafts of mice receiving preactivated hu-PBL. This beta cell injury resulted in impaired glucose tolerance, with in some animals recurrence of hyperglycaemia, and decreased insulin and C-peptide levels after glucose stimulation. Therefore, we conclude that activation of hu-PBL prior to transfer is essential in achieving xenograft infiltration and destruction in hu-PBL-SCID mice. The need for immune manipulation suggests that interactions between hu-PBL and xenografts in this model may be hampered by incompatibilities in cross-species adhesion and/or activation signals.

Animals↗

PubMed1998

SCID mouse models of human stem cell engraftment.

The discovery of the severe combined immunodeficiency (scid) mouse mutation has provided a tool for establishment of small animal models as hosts for the in vivo analysis of normal and malignant human pluripotent hemopoietic stem cells. Intravenous injection of irradiated scid mice with human bone marrow, cord blood, or G-CSF cytokine-mobilized peripheral blood mononuclear cells, all rich in human hemopoietic stem cell activity, results in the engraftment of a human hemopoietic system in the murine recipient. This model has been used to identify a pluripotent stem cell, termed "scid-repopulating cell" (SRC) that is more primitive than any of the hemopoietic stem cell populations identified using the currently available in vitro methodology. In this review, we describe the development and use of this model system, termed Hu-SRC-SCID, and summarize the discoveries that have resulted from the investigation of human stem cells in this model. Finally, we detail the recent extension of the original Hu-SRC-SCID model system based on the C.B-17-scid mouse as the murine host to the Hu-SRC-NOD-SCID model based on the NOD-scid mouse as the host. The engraftment of human stem cells in the Hu-SRC-NOD-SCID model is enhanced over that observed in the Hu-SRC-SCID model and results in exceptionally high levels of human hemopoietic cells in the murine recipient. Future directions to further improve the Hu-SRC-NOD-SCID model system and the potential utility of this model in the preclinical and diagnostic arenas of hematology and oncology are discussed.

Animals↗

PubMed1994

The SCID mouse environment causes immunophenotypic changes in human immature T-cell lines.

In order to evaluate whether the SCID mouse can provide the microenvironment for the growth of human immature T-cell leukemias and if in vivo growth alters their phenotype, we examined the behavior of 3 well-characterized T-cell acute lymphoblastic leukemia (T-ALL)-derived T-cell lines which are at different stages of maturation (CEM, SUP-T3 and MOLT-4f) after transfer to non-irradiated SCID mice. All 3 T-cell lines engrafted and proliferated to form tumors in the mice and showed dissemination patterns in the SCID mouse comparable to those of T-ALL in man: i.e., human cells were detectable by flow cytometry or were cultured from mouse bone marrow, spleen, liver or thymus. CEM, which is the most immature T-cell line, readily formed tumors after injection of cells. The more mature T-cell lines, SUP-T3 and MOLT-4f, required a longer time period, even after injection of higher cell numbers. Whereas no changes in the configuration of the rearranged T-cell receptor genes were detected, striking phenotypic changes were observed in all 3 leukemias growing in the SCID mice after injection. SCID-CEM cells showed an increase in the surface expression of CD3 and CD8 and a decrease in the expression of CD1 and CD71 (transferrin-receptor). SCID-MOLT-4f cells showed an increase in CD5 and CD8 expression and a decrease in CD45RA expression. SCID-SUP-T3 cells showed increased expression of CD8 and CD45RA. Apparently, the mouse environment caused changes in cell-surface antigen expression on the T-ALL-derived T-cell lines. Some immunophenotypic changes remained stable during subsequent growth in culture of SUP-T3 cells, suggesting that maturation of the cell line occurred in vivo. The other cell lines, CEM and MOLT-4f after undergoing in vivo-induced changes, reverted to the original immunophenotype, suggesting transitory activation in vivo. These data point out the importance of stromal factors in defining growth and maturation of human leukemic cells in vivo, in SCID mice.

Animals↗

PubMed2003

The SCID mouse model: novel therapeutic targets - lessons from gene transfer.

The hallmark of rheumatoid arthritis (RA) is progressive destruction of the joints, preceded and accompanied by synovial hyperplasia and chronic inflammation. Spontaneous and induced animal models of RA reflect predominantly the inflammatory aspects of the disease. To reproduce the destruction of cartilage and bone mediated by an activated synovium, it was desirable to develop models that allow the dissection of cellular and molecular components derived from human tissue. The SCID mouse co-implantation model of human RA focuses on RA synovial fibroblasts (RA-SF) and their role in cartilage destruction. The model has provided the best evidence that RA-SF contribute significantly to matrix degradation, even in the absence of human lymphocytes and macrophages, since highly purified RA-SF invade the co-implanted normal human cartilage. Moreover, it became clear that they maintained their aggressive phenotype over long periods of time, particularly at sites of invasion into the co-implanted human cartilage. Targeting different signaling molecules, cytokines and matrix-degrading enzymes by soluble receptors, antagonists or negative mutants in the SCID mouse model of RA has implicated many of them in the mechanisms leading to cartilage destruction. However, since inhibition of a single molecule or pathway is not sufficient to inhibit the aggressive behavior of RA-SF it appears necessary to co-express in the synoviocytes genes for two or even more antagonists of e.g. cytokines, matrix-degrading enzymes or molecules interfering specifically with signaling pathways involved in the apoptosis of RA-SF. Based on the recent observation that the L1 (line-1) endogenous retroviral element appears responsible for the cytokine- independent activation via the MAPK p38delta, the current understanding of disease pathogenesis suggests that both the cytokine-dependent as well as the cytokine-independent pathways of joint destruction must be inhibited. Modulation of both pathways by gene transfer approaches in the SCID mouse model is a feasible method aimed at identifying novel targets for the prevention of cartilage destruction in RA.

Animals↗

PubMed2004

[Development of HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and its immunological features].

OBJECTIVE: To develop a HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and investigate its immunological features. METHODS: Thirty-two CB17SCID mice were randomly divided into 4 groups: group A (5 mice) subcutaneously injected with phosphate-buffered saline, group B (5 mice) intraperitoneally injected with human peripheral blood lymphocyte (PBL) for immune reconstruction, group C (11 mice) subcutaneously injected with human cervical carcinoma cell line SiHa, and group D (11 mice) intraperitoneally injected with PBL and subcutaneously injected with SiHa cells after 24 hours of PBL transplantation. The tumor growth, behaviors and status of xenogeneic graft versus host disease (XGVHD) were observed. Human immunoglobulins G (IgG) in mouse serum, the percentage of human CD3(+), CD4(+) and CD8(+) T cells in peripheral blood and spleen, spleen weight, tumor infiltrating lymphocytes and human CD4(+) T cells, and cytotoxicity test of spleen cells were detected. RESULTS: The rate of successful tumor transplantation was 100%. XGVHD was not found. On the 5th day, human IgG level in the group B (0.98 microg/ml +/- 0.20 microg/ml) and group D (1.39 microg/ml +/- 0.25 microg/ml) was significantly higher than that in the group A (t = 7.655, 9.937, both P = 0.000). Human IgG level in group D was significantly higher than that in the group B (t = 3.200, P = 0.006). Only very low levels of human serumal IgG were detected in the group C and group A with no significantly difference. The level of human serumal IgG was gradually elevated in all the humanized SCID mice as the the time after PBL transplantation went on, and was significantly higher than that in non-humanized mice (P < 0.05). The percentage of human CD3(+), CD4(+) and CD8(+) T cells was significantly increased in the peripheral blood and spleen of immunoreconstituted SCID mice. The weight of spleen was markedly increased in the group D. TIL infiltrating in the tumor were remarkable and human CD4(+) T cells was detected by immunohistochemistry in the group D but not in the group C. The spleen cells in the group D displayed stronger cytotoxicity to the target cells (P < 0.05). CONCLUSION: Human immune function can be successfully reconstructed in SCID mouse via intraperitoneally injecting with human PBL, and induce anti-tumor immune response to the transplantated tumor of HPV16 positive cervical cancer.

Animals↗