Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks / 한국실험동물학회지

In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model.

Comparative study of fertilization rates of C57BL/6NKorl and C57BL/6N mice obtained from two other sources / 한국실험동물학회지

C57BL/6N is the most widely used inbred mouse strain applied in a wide variety of research areas including cancer, cardiovascular biology, developmental biology, diabetes and obesity, genetics, immunology, neurobiology, and sensorineural research. To compare the fertilization rates of C57BL/6NKorl mice with two commercial C57BL/6N stocks, differences in reproductive organ structures, sperm and egg numbers, fertilization rates, and embryo development rates among C57BL/6NKorl (Korea FDA source), C57BL/6NA (USA source), and C57BL/6NB (Japan source) mice were determined. Among the stocks, no significant differences were detected in organ weight and histological structure of male and female reproductive organs, although body weight was higher in C57BL/6NKorl mice than that in the other groups. The concentration and morphology of sperm and eggs in C57BL/6NKorl mice were similar to those of C57BL/6NA and C57BL/6NB mice. Furthermore, the three stocks had similar in vitro fertilization and embryo development rates, although these rates tended to be higher in C57BL/6NB mice. Pup body weight was higher in C57BL/6NKorl and C57BL/6NB mice than that in C57BL/6NA mice. The results of the present study suggest that C57BL/6NKorl, C57BL/6NA, and C57BL/6NB mice obtained from three different sources have similar fertilization and embryo development rates, although there were slight differences in the magnitude of their responses rates.

Use of C57BL/6N mice on the variety of immunological researches / 한국실험동물학회지

Inbred mice are an essential animal strain for research as they can improve the reproducibility and reliability of study results. The establishment of new inbred lines is continuing, and new inbred lines are being used in many research fields. C57BL/6 is a mouse laboratory animal that has been developed and used as an inbred strain since early stage of mouse strain development, and, in the 1950s, C57BL/6 was separated into substrains by the Jackson Laboratory (C57BL/6J) and the National Institutes of Health (C57BL/6N). C57BL/6 mice have been used in immunology and antitumor activity studies since the early strain development stage. After the mouse genome was fully described, C57BL/6 mice use in many areas of research has expanded. In particular, immunological characteristics such as those related to cell-mediated immunity and NK cell activity are relatively higher in C57BL/6 mice than in other mice. The C57BL/6NKorl is a stock of C57BL/6N established as part of a localization of experimental animal strategy of the Korean Food and Drug Administration. Based on analysis of single nucleotide polymorphisms (SNPs), C57BL/6NKorl is considered a genetically distinct inbred stock from other C57BL/6N. Various research efforts have been made to describe the characteristics and increase knowledge of the characteristics of C57BL/6Nkorl. The results obtained through these efforts are expected to increase the utilization of C57BL/6Nkorl as a domestic laboratory animal resource and to enhance the reliability of mouse based studies.

Comparative study of the immunological characteristics of three different C57BL/6N mouse substrains / 한국실험동물학회지

Inbred mice, a systematically developed homogeneous animal, have been developed to maintain experimental reproducibility and to minimize experimental variables in animal-based studies. In particular, C57BL/6 mice are frequently used in experiments into immunology and antitumor activity experiments. This study was compared the immunological characteristics of C57BL/6NKorl, a Korean developed experimental animal resource, with those of two other C57BL/6N substrains. Mouse body, thymus, and spleen weights in C57BL/6NKorl were not significantly different from those of the other two C57BL/6N substrains. Among the three substrains, there was no difference in the distribution of T and B cells, which are lymphocytes involved in adaptive immunity, and no difference in NK cells related to innate immunity. Results for macrophages and granulocytes, which have roles in innate immunity, were similar in all three substrains. In order to investigate the expressions of major histocompatibility complex (MHC) molecules and allogenic antigens, splenocytes were separated from obtained spleen and analyzed by using flow cytometry. MHC class I and II molecules, which are important during self/non-self-discrimination, were similar in the three substrains. In addition, expression of alloantigen involved in allografts showed similar results in the three substrain. Thus, the results of this study provide strong evidence that C57BL/6NKorl is immunologically similar to two other C57BL/6N substrains.

Comparison of humoral and cell-mediated immunity in three different C57BL/6N mouse substrains / 한국실험동물학회지

Adaptive immunity is a type of immune response mediated by T and B cells, and is important response for immune response amplification and memory. In this study, the adaptive immunologic properties of C57BL/6NKorl substrain were compared with those of two other C57BL/6N substrains. There were no significant differences between the C57BL/6NKorl and the two other C57BL/6N substrains in the histological structures of the thymus and spleen, which are immunologic organs containing T cell and B cells. In addition, flow cytometric analysis did not reveal any significant differences in the distribution of T and B cell populations of the three substrains. To evaluate cell-mediated immunity of T cells in the three different substrains, we treated isolated T cells from spleen with Con A. The T cells of C57BL/6NKorl showed Con A-dependent proliferation of T cells at lower cell number than those in T cells from the other two C57BL/6N substrains. B cell-mediated humoral immune responses were not significant different among the three substrains. Thus, the results of this study provide evidence that C57BL/6NKorl mice are similar to those two other C57BL/6N substrains in humoral immunity, but C57BL/6NKorl has stronger response in cell mediated immunity.