черновик. ЧЕРНОВИК. Применение инбредных мышей линий balbc, Nude, C57BL6 в качестве экспериментальных моделей.
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Abstract We examined the effect of adding species-appropriate environmental enrichment items to breeding cages of BALB/cAnNCrl and 129S2/SvPasCrl mice. The 3 enrichment conditions were: 1) cotton nesting material; 2) nesting material plus a paper shelter and rolled paper bedding; and 3) an igloo dome with an exercise wheel in addition to the shelter-group enrichments. We measured litter size, litter survival to weaning age, average pup weight at 21 d, and the interlitter interval to evaluate reproductive performance. A random subset of the first- or second-litter offspring from each enrichment condition and strain was assessed in multiple behavioral tests. Enrichment significantly affected anxiety-like behavior and sociability, with the direction of change dependent on strain and sex. Litter parity had greater effects on some reproductive parameters than did the enrichment condition, and this effect was not solely due to a difference between the first compared with subsequent litters. The significant effects of litter parity on the number of pups born and weaned, female pup weight, and interlitter interval were dependent on the enrichment condition in BALB/c but not 129/Sv mice. Offspring from the first or second litter were included in a generational component to investigate whether enrichment effects on reproduction persist in adult offspring after transfer to a different facility for breeding. Natal cage enrichment had no effect on any reproductive parameter in the transferred mice. Overall, additional enrichment beyond nesting material had a beneficial effect on the interlitter interval in BALB/c mice and on the number of pups weaned in 129/Sv mice. 9. Paladino, N. Characterization of locomotor activity circadian rhythms in athymic nude mice / N. Paladino, J.M. Duhart, M.L. Mul Fedele, D.A. Golombek // J Circadian Rhythms. - 2013. – V. 11. – I. 1. – P. 2. - DOI: 10.1186/1740-3391-11-2. Abstract Background: The relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice. Methods: General activity circadian rhythms in 2–4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light–dark schedule) was analyzed. Results: Free-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light–dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups. Conclusions: Since athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics. 10. Cladel, N.M. Mouse papillomavirus infection persists in mucosal tissues of an immunocompetent mouse strain and progresses to cancer / N.M. Cladel, L.R. Budgeon, K.K. Balogh et al. // Sci Rep. - 2017. – V. 7. – I. 1. – P. 16932. Abstract Mouse papillomavirus has shown broad tissue tropism in nude mice. Previous studies have tested cutaneous infections in different immunocompromised and immunocompetent mouse strains. In the current study, we examined mucosal infection in several immunocompetent and immunocompromised mouse strains. Viral DNA was monitored periodically by Q-PCR of lavage samples. Immunohistochemistry and in situ hybridization were used to determine viral capsid protein and viral DNA respectively. All athymic nude mouse strains showed active infections at both cutaneous and mucosal sites. Interestingly, NOD/SCID mice, which have a deficiency in T, B, and NK cells, showed minimal disease at cutaneous sites but developed persistent infection at the mucosal sites including those of the anogenital region and the oral cavity. Three strains of immunocompetent mice supported mucosal infections. Infections of the lower genital tract in heterozygous (immunocompetent) mice of the NU/J strain progressed to high grade dysplasia and to carcinoma in situ. Anti-MmuPV1 neutralizing antibodies were detected in the sera of all immunocompetent animals. Our findings demonstrate that the mucosae may be the preferred sites for this virus in mice. The mouse model is expected to be a valuable model for the study of mucosal papillomavirus disease, progression, and host immune control. 11. Economopoulos V. Comparing the MRI appearance of the lymph nodes and spleen in wild-type and immuno-deficient mouse strains / V. Economopoulos, J.C Noad, S. Krishnamoorthy, B.K. Rutt, P.J. Foster // PLoS One. - 2011. – V. 6. – I. 11: e27508. - DOI: 10.1371/journal.pone.0027508. Abstract The goal of this study was to investigate the normal MRI appearance of lymphoid organs in immuno-competent and immuno-deficient mice commonly used in research. Four mice from each of four different mouse strains (nude, NOG, C57BL/6, CB-17 SCID (SCID)) were imaged weekly for one month. Images were acquired with a 3D balanced steady state free precession (bSSFP) sequence. The volume of the lymph nodes and spleens were measured from MR images. In images of nude and SCID mice, lymph nodes sometimes contained a hyperintense region visible on MRI images. Volumes of the nodes were highly variable in nude mice. Nodes in SCID mice were smaller than in nude or C57Bl/6 mice (p<0.0001). Lymph node volumes changed slightly over time in all strains. The spleens of C57Bl/6 and nude mice were similar in size and appearance. Spleens of SCID and NOG mice were significantly smaller (p<0.0001) and abnormal in appearance. The MRI appearance of the normal lymph nodes and spleen varies considerably in the various mouse strains examined in this study. This is important to recognize in order to avoid the misinterpretation of MRI findings as abnormal when these strains are used in MRI imaging studies. 12. Ji D.B. Anti-tumor effect of Liqi, a traditional Chinese medicine prescription, in tumor bearing mice / D.B. Ji, J. Ye, Y.M. Jiang, B.W. Qian BMC Complement Altern Med. – 2009. -V. 9. – P. 20. – DOI: 10.1186/1472-6882-9-20 Abstract Background: Liqi, an herbal preparation used in traditional Chinese medicine, has been used to treat cancer in China for centuries. We investigated the anti-tumor effects of liqi and their mechanisms in mice that had been xenografted with tumors. Methods: Sarcoma 180 tumor, Lewis lung carcinoma, and SGC-7901 cells were implanted in BALB/c mice, C57BL/6 mice, and BALB/c nude mice, respectively. Liqi was administered to subgroups of these mice. The tumor weight and size were measured. Cell cycle analysis and T lymphocyte subsets were determined by flow cytometry. The activity of NK cells and TNF was tested using cytotoxicity assay on YAC-1 cells and L929 cells, respectively, and the activity of IL-2 was tested with an IL-2-dependent CTLL-2 cell proliferation assay. Platelet aggregation was monitored by measuring electric impedance, and the levels of thromboxane A2 (TXA2) and prostacyclin (PGI2) in blood were measured by 125I-TXB2 and 125I-Keto-PGF1α radioimmunoassay. Results: The results showed that liqi inhibited tumor growth in tumor-implanted mice and arrested the cell proliferation in the G0/G1 phase and reduced the portion of cells in S and G2/M phase for SGC-7901 cells. Liqi increased the activity of NK cells and TNF-α, stimulated IL-2 production and activity, and regulated T lymphocyte subpopulations. Liqi inhibited the Lewis lung carcinoma metastasis by inhibiting platelet aggregation and normalizing the balance between TXA2 and PGI2. Conclusion: All these findings demonstrated that liqi has an anti-tumor effect in vivo. The mechanism may be related to immune regulation and anticoagulation effects. 13. Sin S.H. Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections / S.H. Sin, A.B. Eason, R. Bigi, et al. // J Virol. – 2018. – V. 92. – I. 19: e01138-18. - DOI: 10.1128/JVI.01138-18. ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) induces B cell hyperplasia and neoplasia, such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogramming in vivo, we expressed the KSHV latency locus, inclusive of all viral microRNAs (miRNAs), in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia. This phenotype was ameliorated by everolimus, which is a rapamycin derivative used for the treatment of mantle cell lymphoma. KSHV latency mice exhibited hyperresponsiveness to the T-dependent (TD) antigen mimic anti-CD40 and increased incidence of pristane-induced inflammation. Lastly, the adaptive immunity against a secondary infection with Zika virus (ZIKV) was markedly enhanced. These phenotypes are consistent with KSHV lowering the activation threshold of latently infected B cells, which may be beneficial in areas of endemicity, where KSHV is acquired in childhood and infections are common. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latency in B cells and is stringently linked to primary effusion lymphoma (PEL) and the premalignant B cell hyperplasia multicentric Castleman's disease (MCD). To investigate potential genetic background effects, we expressed the KSHV miRNAs in BALB/c transgenic mice. BALB/c mice are the preferred strain for B cell hybridoma development because of their propensity to develop predictable B cell responses to antigen. The BALB/c latency mice exhibited a higher incidence of B cell hyperplasia as well as sustained hyperglobulinemia. The development of neutralizing antibodies against ZIKV was augmented in BALB/c latency mice. Hyperglobulinemia was dampened by everolimus, a derivative of rapamycin, suggesting a role for mTOR inhibitors in managing immune activation, which is hallmark of KSHV infection as well as HIV infection. 14. Chuang M.H. The Chinese medicine JC-001 enhances the chemosensitivity of Lewis lung tumors to cisplatin by modulating the immune response / M.H. Chuang, M.S. Jan, J.T. Chang, F.J. Lu // BMC Complement Altern Med. – 2017. – V. 17. – I. 1. – P. 210. - DOI: 10.1186/s12906-017-1728-x Abstract Background: JC-001 is a Chinese medicine that can modulate the immunity in Hepa 1-6 tumor-bearing mice, and we questioned whether JC-001 can serve as efficient adjuvant chemotherapy. We aimed to identify a novel approach for enhancing cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy by immunomodulation. Methods: The anti-tumor activity in vitro was determined based on foci formation and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A LLC1 tumor xenograft model was used to analyze the activity of tumor rejection in vivo. The tumors were analyzed through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) staining and cytokine arrays. Results: JC-001 suppressed foci formation and reduced the viability of Lewis lung carcinoma (LLC1) cells in vitro. JC-001 suppressed LLC1 tumor growth in immunodeficient BALB/c nude mice and in immunocompetent C57BL/6 mice to an even greater extent. Furthermore, JC-001 up-regulated interferon-γ expression in the tumor microenvironment, enhanced the Th1 response in tumor-bearing mice, and increased the chemosensitivity of LLC1 tumors to CDDP chemotherapy. The results of our study suggest that JC-001 is associated with low cytotoxicity and can significantly suppress tumor growth by enhancing the Th1 response. Conclusion: JC-001 is a Chinese medicine with potential clinical applications in CDDP-based chemotherapeutic regimens. Electronic supplementary material: The online version of this article (doi:10.1186/s12906-017-1728-x) contains supplementary material, which is available to authorized users. 15. Ren L. Evaluation of Su Fu'ning Lotion's Inhibitory Effects on Bladder Cancer Cells In Vitro and In Vivo by Intravesical Instillation / L. Ren, X. Yang, L. Zhao, H. Zhang, J. Wang // Integr Cancer Ther. – 2016. – V. 15. – I. 1. – P. 80-86. – DOI: 10.1177/1534735415596569. Abstract Background: Bladder cancer is a common malignant tumor with a very high recurrence rate after surgery. Intravesical instillation can help clear up the residual tumor cells after surgery and thereby reduce the recurrence rate. Objective. To establish a bladder tumor transplantation animal model and to evaluate the inhibitory effects of a novel perfusate, Su Fu’ning Lotion (SFN), on bladder tumor. Methods. SFN was compared with several commonly used chemotherapy drugs, including mitomycin (MMC) and pirarubicin (THP) for anticancer effects on the bladder cancer cell lines T24, BTT, and BIU-87 and SFN half inhibitory concentrations (IC50) were determined after 48 hours of treatment. In addition, bladder cancer orthotopic transplantation tumor models were established in BALB/C nude mice and T739 mice, and SFN anticancer effects were assessed in vivo, with normal saline and MMC as negative and positive controls, respectively. Results. SFN, MMC, and THP were all lethal to bladder cancer cells, in vitro, with SFN and THP significantly superior to MMC. IC50 values for SFN were 13.22, 11.22, and 12.5 µg/mL on T24, BTT, and BIU-87 cells, respectively. In vivo, SFN significantly reduced the mouse bladder wet weight and prolonged the animal survival compared with controls (P < .05), suggesting that SFN significantly inhibited T24/BTT cell growth in mice. Conclusion. SFN inhibited the bladder cancer cell proliferation in vitro and in vivo and significantly prolonged the survival of mice with bladder cancer xenografts, indicating that SFN could be used as a perfusate after surgery for removal of residual bladder cancers cells. 16. Candolfi M. Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression / M. Candolfi, J.F. Curtin, W.S. Nichols, et al. // J Neurooncol. – 2007. – V. 85. – I. 2. P. 133-148. Abstract Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP− and vimentin+. Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain. 17. Bleul T. Different Innate Immune Responses in BALB/c and C57BL/6 Strains following Corneal Transplantation / T. Bleul, X. Zhuang, A. Hildebrand et al. // J Innate Immun. –2021. – V. 13. – I. 1. – P. 49-59. Abstract Purpose: To investigate immunological differences and the role of CD38+/F4/80 + M1 macrophages in C57BL/6J- and BALB/c-recipient mouse corneal transplantation models. Methods: Allogeneic transplantation was performed crosswise in BALB/c mice and C57BL/6J mice; syngeneic transplantation was performed in both strains. Anterior chamber depth (ACD) was measured before and central corneal thickness (CCT) was measured both before and after transplantation. In vivo graft rejection was monitored using anterior eye segment optical coherence tomography (ASOCT) evaluating the CCT and grading of corneal oedema using a well-established clinical score (CS). Histology of corneal grafts was performed 18 or 21 days after surgery. Immunohistochemistry with anti-F4/80 antibody and anti-CD38 antibody was used for detecting M1 macrophages within the grafts. |