Background: To determine whether the background of BALB/c substrains affects the response to anti-tumor drugs, we measured for alterations in tumor growth, histopathological structure of the tumor, and expressions of tumorrelated proteins in three BALB/c substrains derived from different sources (BALB/cKorl, BALB/cA and BALB/cB), after exposure to varying concentrations of cisplatin (0.1, 1 and 5 mg/kg). Results: Cisplatin treatment induced similar responses for body and organ weights, serum analyzing factors, and blood analyzing factors in all BALB/c substrains with CT26 syngeneic tumor. Few differences were detected in the volume and histopathological structure of the CT26 tumor. Growth inhibition of CT26 tumors after exposure to cisplatin was greater in the BALB/cB substrain than BALB/cKorl and BALB/cA substrains, and a similar pattern was observed in the histopathological structure of tumors. However, the expression levels of other tumor-related factors, including Ki67, p27, p53, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3 (Cas-3), matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) proteins, were constantly maintained in the tumors of all three substrains after cisplatin treatment. A similar decrease pattern was observed for the expressions of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and IL-10, in the CT26 tumors of the three BALB/c substrains. Conclusions Taken together, results of the present study indicate that the genetic background of the three BALB/c substrains has no major effect on the therapeutic responsiveness of cisplatin, except growth and histopathology of the CT26 syngeneic tumor.

Background: Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results: Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.

Background: As a laboratory animal resource, the ICR mouse is commonly used in a variety of research fields. However, information on differences in exercise-related characteristics in ICR mice derived from different lineages and the underlying mechanisms remains to be elucidated. In this study, we investigated the intrinsic exercise capacity and a magnitude of response to acute exercise, and sought to identify mechanisms contributing to difference in Korl:ICR (a novel ICR lineage recently established by the National Institute of Food and Drug Safety Evaluation, Korea) and two commercialized ICR lineages derived from different origins (viz., A:ICR mouse from Orient Bio Com, the United States, and B:ICR mouse from Japan SLC Inc., Japan). Results: Results showed that despite no significant difference in body weight and weight-proportioned tissue mass of heart and skeletal muscles among groups, the relatively low intrinsic exercise capacity and exaggerated response to acute exercise were identified in B:ICR comparted with Korl:ICR and A:ICR, as reflected by total work and lactate threshold (LT). Also, the mitochondrial efficiency expressed as the complex 1 and complex 1 + 2 respiratory control ratio (RCR) values for cardiac mitochondrial O 2 consumption in B:ICR was significantly lower than that in Korl:ICR with higher level of state 2 respiration by glutamate/malate and UCP3 expression in cardiac muscle. Conclusions Taken together, these results indicate that the intrinsic exercise capacity of ICR mouse varies according to lineages, suggesting the role of cardiac mitochondrial coupling efficiency as a possible mechanism that might contribute to differences in the intrinsic exercise capacity and magnitude of response to exercise.

Background: Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results: Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/ 2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.

Background: As a laboratory animal resource, the ICR mouse is commonly used in a variety of research fields. However, information on differences in exercise-related characteristics in ICR mice derived from different lineages and the underlying mechanisms remains to be elucidated. In this study, we investigated the intrinsic exercise capacity and a magnitude of response to acute exercise, and sought to identify mechanisms contributing to difference in Korl:ICR (a novel ICR lineage recently established by the National Institute of Food and Drug Safety Evaluation, Korea) and two commercialized ICR lineages derived from different origins (viz., A:ICR mouse from Orient Bio Com, the United States, and B:ICR mouse from Japan SLC Inc., Japan). Results: Results showed that despite no significant difference in body weight and weight-proportioned tissue mass of heart and skeletal muscles among groups, the relatively low intrinsic exercise capacity and exaggerated response to acute exercise were identified in B:ICR comparted with Korl:ICR and A:ICR, as reflected by total work and lactate threshold (LT). Also, the mitochondrial efficiency expressed as the complex 1 and complex 1 + 2 respiratory control ratio (RCR) values for cardiac mitochondrial O 2 consumption in B:ICR was significantly lower than that in Korl:ICR with higher level of state 2 respiration by glutamate/malate and UCP3 expression in cardiac muscle. Conclusions Taken together, these results indicate that the intrinsic exercise capacity of ICR mouse varies according to lineages, suggesting the role of cardiac mitochondrial coupling efficiency as a possible mechanism that might contribute to differences in the intrinsic exercise capacity and magnitude of response to exercise.

Differences in responsiveness of BALB/c substrains have been investigated in various fields, including diabetes induction, corpus callosum deficiency, virus-induced demyelinating disease, aggressive behavior and osteonecrosis. However, induction efficacy of skin tumor remains untried. We therefore investigated the influence of BALB/c substrain backgrounds on the skin tumor induction efficacy in response to DMBA (7,12-Dimethylbenz[a]anthracene) and TPA (12-O-tetradecanoylphorbol-13-acetate) cotreatment. Alterations in the levels of tumor growth related factors, histopathological structure, and the expression to tumor related proteins were measured in three BALB/c substrains (BALB/cKorl, BALB/cA and BALB/cB) after exposure to DMBA (25 μg/kg) and three different doses of TPA (2, 4 and 8 μg/kg). The average number and induction efficacy of tumors in response to DMBA+TPA treatment were significantly greater in the BALB/cKorl substrain than in BALB/cA and BALB/cB. However, cotreatment with DMBA+TPA induced similar responses for body and organ weights of all three substrains. Few differences were detected in the serum analyzing factors, while similar responsiveness was observed for blood analyzing factors after DMBA+TPA treatment. Furthermore, the three BALB/c substrains exhibited similar patterns in their histopathological structure in DMBA+TPA-induced tumors. The expression levels of apoptotic proteins and tumor related proteins were constantly maintained in all three BALB/c substrains treated with DMBA+TPA. In addition, the responsiveness to cisplatin treatment was overall very similar in the three BALB/c substrains with DMBA+TPA-induced tumors. Taken together, these results indicate that genetic background of the three BALB/c substrains does not have a major effect on the DMBA+TPA-induced skin carcinogenesis and therapeutic responsiveness of cisplatin, except induction efficacy.

C57BL/6NKorl mice are a novel mouse stock recently developed by the National Institute of Food and Drug Safety Evaluation in Korea. Extensive research into the nature of C57BL/6NKorl mice is being conducted. However, there is no scientific evidence for the phenotypic response to restraint stress (RST), a stress paradigm for modeling depressive disorders, in rodents. In this study, we investigated the repeated RST-induced depressive-like phenotypes in C57BL/6 N mouse substrains (viz., C57BL/6NKorl mice from Korea, C57BL/6NA mice from the United States, and C57BL/6NB mice from Japan) obtained from different sources. The results showed that C57BL/6 N mice derived from various sources exposed to repeated RST resulted in depressive-like phenotypes reflected by a similar degree of behavioral modification and susceptibility to oxidative stress in a duration-dependent manner, except for the distinctive features (increased body weight (BW) and tolerance to the suppression of BW gain by exposure to repeated RST) in C57BL/6NKorl mice. Taken together, the duration-dependent alteration in depressive-like phenotypes by repeated exposure to RST observed in this study may provide valuable insights into the nature of C57BL/6NKorl mice as an alternative animal resource for better understanding of the etiology of depressive disorders and the mechanisms of antidepressant actions.

The kainic acid-induced seizure mouse model is widely used in epilepsy research. In this study, we applied kainic acid to the subcutaneous injections of three different sources of DBA/2 mice to compare and evaluate the seizure response. The three mouse sources consisted of DBA/2Kor1 (Korea FDA source), DBA/2A (USA source), and DBA/2 (Japan source), and were purchased from different vendors. To compare the responses of DBA/2 mice to kainic acid injections, we examined the survival rate, seizure phenotype scoring, and behavioral changes. We also evaluated brain lesions using histopathological analysis. Following the administration of kainic acid, almost half of the cohort survived, and the seizure phenotype displayed a moderate level of sensitivity (2 ~ 4 out of 6). In the histopathologic analysis, there was no change in morphological features, and levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) increased in the kainic acid-treated groups. However, there was no difference in the neuronal nuclei (NeuN) expression level. All the data showed that the responses in the kainic acid-treated group were similar across the three strains. In conclusion, our results suggest that the three sources of DBA/2 mice (DBA/2Kor1, DBA/2A, and DBA/2B) have similar pathological responses to kainic acid-induced seizures.