Comparison of toxic responses to acetaminophen challenge in ICR mice originating from different sources / 한국실험동물학회지

Acetaminophen (APAP) is the most common antipyretic analgesic worldwide. However, APAP overdose causes severe liver injury, especially centrilobular necrosis, in humans and experimental animals. At therapeutic dosage, APAP is mainly metabolized by sulfation and glucuronidation, and partly by cytochrome P450–mediated oxidation. However, APAP overdose results in production of excess reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by cytochromes P450; NAPQI overwhelms the level of glutathione (GSH), which could otherwise detoxify it. NAPQI binds covalently to proteins, leading to cell death. A number of studies aimed at the prevention and treatment of APAP-induced toxicity are underway. Rats are more resistant than mice to APAP hepatotoxicity, and thus mouse models are mainly used. In the present study, we compared the toxic responses induced by APAP overdose in the liver of ICR mice obtained from three different sources and evaluated the usability of the Korl:ICR stock established by the National Institute of Food and Drug Safety Evaluation in Korea. Administration of APAP (300 mg/kg) by intraperitoneal injection into male ICR mice enhanced CYP2E1 protein expression and depleted hepatic GSH level 2 h after treatment accompanied with significantly increased level of hepatic malondialdehyde, a product of lipid peroxidation. Regardless of the source of the mice, hepatotoxicity, as evidenced by activity of serum alanine aminotransferase, increased from 8 h and peaked at 24 h after APAP treatment. In summary, hepatotoxicity was induced after the onset of oxidative stress by overdose of APAP, and the response was the same over time among mice of different origins.

Staphylococcus sciuri associated to subcutaneous abscess and dermatitis in ICR mouse / Staphylococcus sciuri associado a abcesso subcutâneo e dermatite em ratos

Subcutaneous mass was found in ICR mouse during daily health observation in the breeding colony of the National Laboratory Animal Center, Mahidol University, Thailand. The animal was subsequently culled and humanely sacrificed due to the institutional preventive medicine policy. Microbiological and histopathological studies were performed for definitive diagnosis. The results described that the case was subcutaneous abscess and chronic dermatitis in association with Staphylococcus sciuri infection without epizootic and mortality. This was determined as the first reported case in Thailand occurring in mouse. Reproductive stress and abrasion skin wound may be the predisposing factors. Although pathogenic staphylococci in laboratory animals are limited to S. aureus and S. xylosus, S. sciuri opportunistic properties, natural history, and heterogeneity should not be forgotten.(AU)

Uma massa subcutânea foi encontrada em um rato ICR durante uma observação diária de saúde na colônia reprodutora do Laboratório do Centro Animal Nacional, na Universidade de Mahidol, Tailândia. O animal foi selecionado e humanamente sacrificado devido à política institucional de medicina preventiva. Estudos microbiológicos e histopatológicos foram realizados para um diagnóstico definitivo. Os resultados descrevem que o caso foi um abcesso subcutâneo e dermatite crônica associado com infecção por Staphylococcus sciuri sem epizootia e mortalidade. Este foi determinado como o primeiro caso relatado em ratos na Tailândia. Estresse reprodutivo e ferida abrasiva na pele podem ser os fatores de predisposição. Apesar de staphylococci patogênicos em animais de laboratório serem limitados a S. aureus E S. xylosus, as propriedades oportunistas, história natural e heterogeneidade do S. sciuri não devem ser esquecidos.(AU)

Establishment of first mandibular molar development of the time sequence in ICR mice / 中国比较医学杂志

Objective This study aims to understand the characteristics of the time sequence of ICR mouse first mandibular molar tooth germ development through dynamic observation.Methods Tooth germ of Embryos (E11.5,E12.5,E13.5,E14.5,E15.5,E16.5,E17.5 and E18.5) and postnatal (PN1,PN2) mice were obtained.The heads (E11.5-E15.5) and mandibles (E16.5-PN2) of mice were dissected,fixed and embedded for serial sections and HE staining.All the results were assessed under light microscopy.Results The tooth germ underwent various development stages including the bud,cap and bell stages.Mouse odontogenesis was initiated at E11.5.Proliferation of oral epithelium formed the bud stage at E13.5.Then the cap stage was observed at E14.5-E15.5 and the bell stage was appeared beginning from E16.5.The pre-dentin was observed at PN1,as well as the dentin at PN2.Conclusions Establishing the regular development pattern of the first mandibular molar of ICR mice will provide a reliable basis for the future use in the specific tooth germ developmental research.

Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources / 한국실험동물학회지

Doxorubicin is a widely used chemotherapeutic agents and is now part of standard therapeutic regimens for a variety of cancers (eg, hematopoietic malignancies and advanced solid tumors of the breast, ovary, thyroid, and bone). However, a potentially lethal and dose-dependent cardiotoxicity that appears within a short time after treatment limits the usage of doxorubicin in cancer patients. Although the mechanism of doxorubicin-induced cardiotoxicity is not completely understood, it is thought that free radical-induced oxidative stress and excessive production of reactive oxygen species are primary drivers of its toxicity. In this study, we compared the doxorubicin-induced cardiotoxicity of ICR mice obtained from three different sources and evaluated the utility of Korl:ICR stock established by the Korean FDA. Because doxorubicin-induced cardiotoxicity is thought to involve the excessive generation of ROS followed by oxidative stress, we determined the representative tissue index of oxidation, lipid peroxidation, and antioxidant, glutathione (GSH), as well as the parameters of heart injury. Doxorubicin treatment successfully induced cardiotoxicity as evidenced by histological examination and serum parameters (eg, levels of LDH and CK activities) in ICR mice. It was accompanied by increased lipid peroxidation and a decrease in both cysteine and GSH, further supporting previous reports that oxidative stress is a potential mechanism of doxorubicin-induced cardiotoxicity. Of interest, we did not observe a significant difference in doxorubicin-induced cardiotoxicity among mice of different origins. Collectively, our results suggest that Korl:ICR strain may be useful in the research of doxorubicin-induced cardiotoxicity.

Annual tendency of research papers used ICR mice as experimental animals in biomedical research fields / 한국실험동물학회지

Institute of Cancer Research (ICR) mice have been widely used in various research fields including toxicology, oncology, pharmacology, and pharmaceutical product safety testing for decades. However, annual tendency of research papers involving ICR mice in various biomedical fields has not been previously analyzed. In this study, we examined the numbers of papers that used ICR mice as experimental animals in the social science, natural science, engineering, medicine-pharmacy, marine agriculture-fishery, and art-kinesiology fields by analyzing big data. Numbers of ICR mouse-used papers gradually increased from 1961 to 2014, but small decreases were observed in 2015 and 2016. The largest number of ICR-used papers were published in the medicine-pharmacy field, followed by natural science and art-kinesiology fields. There were no ICR mouse-used papers in other fields. Furthermore, ICR mice have been widely employed in cell biology studies within the natural science field as well as in biochemistry and pathology in the medicine-pharmacy field. Few ICR mouse-used papers were published in exercise biochemistry and exercise nutrition in the art-kinesiology field. Regardless in most fields, the total numbers of published papers involving ICR mice were higher in 2014 than in other years, although the numbers in some fields including dentistry, veterinary science, and dermatology were high in 2016. Taken together, the present study shows that various ICR stocks, including Korl:ICR mice, are widely employed as experimental animals in various biomedical research fields.

Evaluation of antibacterial and therapeutic effects of egg-white lysozyme against Salmonella Typhimurium in ICR mice infected with Salmonella Typhimurium

Salmonellosis is a major bacterial zoonosis that causes self-limited enteritis in animals and foodborne disease and typhoid fever in humans. Recently, multi-drug-resistant strains of Salmonella spp. have increased and caused more serious problems in public health. The present study investigated the antibacterial effects of egg-white lysozyme (EWL) against Salmonella (S.) Typhimurium and the therapeutic effects of EWL for murine salmonellosis. Evaluation of the antibacterial effects of EWL against S. Typhimurium revealed a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EWL of 6.25 and 300 µg/mL, respectively. In the bacterial growth inhibition test, EWL at 300 (p < 0.05) and 600 µg/mL (p < 0.01) significantly inhibited the growth of S. Typhimurium at 4 h postincubation. EWL administration at MIC (LYS-1), MBC (LYS-2) and 2× MBC (LYS-3) for 14 days resulted in mortality of mice infected with S. Typhimurium of 70, 40 and 10%, respectively, while that of control mice (CON) was 90%. Counts of S. Typhimurium in murine spleens were significantly lower in LYS-2 and LYS-3 than CON (p < 0.05). The results of this study indicate that EWL has the potential for treatment of ICR mice infected with S. Typhimurium.

The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet

BACKGROUND/OBJECTIVES: The present study was conducted to investigate the effects of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on obesity and lipid profiles in mice fed a high-fat diet. MATERIALS/METHODS: Forty two ICR mice were randomly divided into six groups. The normal group was fed a basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The normal and HFD groups were also orally administered distilled water each day for 7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0 g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity and lipid profile improvement effects, body and visceral tissue weight, lipid profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. RESULTS: Both MCA and MCE significantly decreased body and visceral tissue weight relative to those of the HFD group (P < 0.05). Additionally high doses of MCE and MCA significantly reduced the plasmatic insulin levels compared to the HFD groups (P < 0.05) to concentrations comparable to those found in the normal group. MCA and MCE supplementation also significantly modulated the lipid profiles in plasma, liver, and feces compared to mice fed the HFD (P < 0.05). Furthermore MCA and MCE significantly increased hepatic SOD activity, and reduced MDA generation in the liver of the HFD mice (P < 0.05). CONCLUSIONS: Results from the present study suggest that Momordica charantia extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism.

Impact of different mouse blastocyst donors on the efficiency of germline chimera production from C57BL/6 embryonic stem cells / 中国实验动物学报

Objective To improve the gene targeting efficiency with C57BL/6 embryonic stem ( ES) cells.Meth-ods Three different genetically modified C57BL/6 ES cell lines, named TLX3, Ai3K and SL, were microinjected into ICR, B6( Cg)-Tyrc-2J and BALB/c mouse blastocysts, respectively.The efficiency was statistically evaluated according to three aspects:blastocyst collection, chimera production and germline transmission.Results None of the three ES cell lines was germline transmitted with B6(Cg)-Tyrc-2J mice as blastocyst donors, while it was achieved with both BALB/c and ICR mouse blastocysts.Compared in the aspect of blastocysts collection, ICR mouse was much better than BALB/c mouse (P<0.05), and the chimera production efficiency of ICR mouse was comparable to that of BALB/c mouse (P =0.115). As to the germline transmission efficiency, that of BALB/c mice is significantly higher than that of the ICR mice ( P<0.01).Conclusions The germline transmission efficiency of BALB/c mouse is highest among these three mouse strains. However, it has the disadvantages of blastocyst collection, developmental delay and zona pellucida fragility, compared with ICR mouse.Therefore, ICR mouse is also a good candidate as blastocyst donor for embryonic stem cell microinjection.

Cronobacter sakazakii Infection Induced Fatal Clinical Sequels Including Meningitis in Neonatal ICR Mice / 한국실험동물학회지

Cronobacter sakazakii (C. sakazakii), formerly Enterobacter sakazakii, is an emerging pathogen associated with the ingestion of contaminated reconstituted formula that causes serious illnesses such as bacteremia, septicemia, necrotizing enterocolitis, meningitis and death in low-birth-weight preterm neonatal infants. The objective of this study was to develop an animal model for human neonatal C. sakazakii infections. We acquired timed-pregnant ICR mice and allowed them to give birth naturally. On postnatal day 3.5, each pup was administered orally a total dose of approximately 107 CFU C. sakazakii strain 3439. Mice were observed twice daily for morbidity and mortality. At postnatal day 10.5, the remaining pups were euthanized, and brain, liver, and cecum were excised and analyzed for the presence of C. sakazakii. C. sakazakii was isolated from cecum and other tissues in inoculated mice. In the tissues of C. sakazakii infected mice, meningitis and gliosis were detected in brain. In this study, we confirmed the neonatal ICR mice may be used a very effective animal model for human neonatal C. sakazakii infections.

Comparison of mouse lung fibrosis induced by intraperitoneal injection and intratracheal instillation of bleomycin / 中国免疫学杂志

Objective:To study the differences of bleomycin-induced pulmonary fibrosis in mice induced by intraperitoneal injection and intratracheal instillation of bleomycin.Methods:ICR mice (male,8 w of age,18 to 22 g bodyweight) were used.①ICR mice were randomly divided into three groups.In the group P,bleomycin was injected intraperitoneal five times in a dose of 40 mg/kg,and in the group I,bleomycin was instilled intratracheally in a dose of 5 mg/kg.The mice were killed at 14,28 or 40 day.②ICR mice were randomly divided into four groups : bleomycin was injected intraperitoneal three,four or five times in a dose of 40 mg/kg,and in the group control ,bleomycin was injected intraperitoneal in a dose of 200 μl for five times.The mice was killed at 28 or 40 day.The pathological changes and symptoms were observed.Results:① The weight of the mice given blemycine were lost after injection.Symptoms were more serious in group P than those of group I.The pulmonary coefficient of group P was more than that of group I.At 28 day after injection,fibrosis was widely and stably formed mainly in around the bronchia and bronchioles,especially,near the pulmonary hilar area,in the group I mice,however,the same changes were mainly seen under the pleura or perivascular pulmonary tissues in the mice of group P.The pathological score of pulmonary fibrosis was different between those two groups.②Different dose of bleomycine induced different change of the mouse's weight.The most of all of the three group were five time injection; The lung index of five time injection of bleomycine was the most.The pulmonary fibrosis mouse model was made successfully.After comparising all of the data,we found intraperitoneal of bleomycine five times was the more convenient method.Conclusion:The sites of pulmonary fibrosis in the mice are different between the mice induced by intraperitoneal injection or intratracheal instillation of bleomycin.Intraperitoneal injection five times is a more convenient method to make pulmonary fibrosis.

Cytotoxic and genotoxic effects of Br-containing oxaphosphole on Allium cepa L. root tip cells and mouse bone marrow cells

The continuous production and release of chemicals into the environment has led to the need to assess their genotoxicity. Numerous organophosphorus compounds with different structures have been synthesized in recent years, and several oxaphosphole derivatives are known to possess biological activity. Such chemical compounds may influence proliferating cells and cause disturbances of the genetic material. In this study, we examined the cytotoxicity and genotoxicity of 4-bromo-N,N-diethyl-5,5-dimethyl-2,5-dihydro-1,2-oxaphosphol-2-amine 2-oxide (Br-oxph). In A. cepa cells, Br-oxph (10-9 M, 10-6 M and 10-3 M) reduced the mitotic index 48 h after treatment with the two highest concentrations, with no significant effect at earlier intervals. Mitotic cells showed abnormalities 24 h and 48 h after treatment with the two lowest concentrations but there were no consistent changes in interphase cells. Bone marrow cells from mice treated with Br-oxph (2.82 x 10-3 µg/kg) also showed a reduced mitotic index after 48 h and a greater percentage of cells with aberrations (principally chromatid and isochromatid breaks). These findings indicate the cytotoxicity and genotoxicity of Br-oxph in the two systems studied.

The establishment of the model in ICR mice with B16 melanoma of C57BL/6 mice / 医学研究生学报

Objectives: To establish melanoma models of B16 cell line in ICR mice. Methods: Inoculating B16 Melanoma cells in ICR mice's feet, back, abdomen and caudal vein, to establish transplanted and metastatic melanoma models. We observed the morphologic characteristics and examined the pathological parameters of melanoma. We analyzed the relations between the number of B16 cells inoculated and the genesis of tumors, the influence of tumor growth on mice's behavior,and growth curve of the melanoma. Results:Six days later, sesamoid, linear and nodal even kaulifloweroid melanoma were seen gradually in ICR mice's feet, back, abdomen and lung (anatomid) after inoculating. The bearing tumor rates have a positive relation to the number of inoculated B16 cells. The rates of bearing tumor was near 100%, after inoculating with 5?10 6 B16 cells. Conclusions: The B16 melanoma cell line derived from C57/B16 mice(black ) has high rates of bearing tumor in ICR mice (white). The B16 melanoma models in ICR mice are ideal tumor models that have the characteristics of easy established,easy observing and easy obtaining.

Dose-Incidence Relationships on the Prenatal Effects of Gamma-Radiation in Mice

The objective of this investigation was to evaluate dose-incidence relationships on the prenatal effects of gamma-radiation. Pregnant ICR mice were exposed on day 11.5 after conception, coincident with the most sensitive stage for the induction of major congenital malformations, with 0.5-4.0 Gy of gamma-radiations. The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, change in head size and any other morphological abnormalities. With increasing radiation dose, incidence of small head, growth retarded fetuses, cleft palate, dilatation of cerebral ventricle and abnormalities of the extremities in live fetuses rose. The threshold doses of radiation that induced cleft palate and dilatation of cerebral ventricle, and abnormal extremities were between 1.0 and 2.0 Gy, and between 0.5 and 1.0 Gy, respectively.

Role of Leukemia Inhibitory Factor in the Effect of Co-Culture on Preimplantation Embryo Develpement / 대한산부인과학회잡지

OBJECTIVE: To assess the effect of recombinant human leukemia inhibitory factor on in vitro development of 1-cell ICR mouse embryo. MATERIALS AND METHOD: ICR mice were superovulated with PMSG/hCG and 1-cell stage mouse embryos were recruited. 1-cell mouse embryo were cocultured on human oviductal cells in a CO2 incubator (coculture group) and were cultured on 0.4% BSA+HTF media (control group). And anti-hLIF Ab was added the cocultured group in a different concentration (1pg, 10pg, 100pg, 1ng) and developmental rate was compaired to the control group, and rhLIF was added to the preincubated 0.4% BSA+HTF media in a different concentration (2000U, 1000U, 100U, 10U) and its developmental rate was compaired to group which was cultured on 0.4% BSA+HTF media only. RESULT: 1. The cleavage rate of 2-cell mouse embryo co-cultured with human tubal epithelial cell was significantly higher than that of cultured with media alone (HTF with 0.4% BSA) (p<0.05). 2. When LIF antibody was added to the medium with human tubal epitherlial cell, the mouse embryo could not cleave more than 2-cell in 1 ng of LIF antibody, and less than 1 ng, the cleavage rate was lower than cultured without LIF antibody group(p<0.05). 3. Two cell blocked ICR mouse embryos were developed into four cells under LIF(p<0.05), but no further development was observed. CONCLUSIONS: These results shows that LIF enhances the development of preimplantation embryo, and when rhLIF is applicated in vitro, it has positive effects on the development of early mouse embryo and can help overcoming the two-cell block.