• Toxicological Research
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• v.21 no.4
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• pp.361-365
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• 2005

This study was conducted to obtain the acute information of the oral dose toxicity of Polycan - originated from Aureobasidium pullulans SM-2001 (half of the dry material is -1,3/1,6-glucans), a UV induced mutant of A. pullulans, having various pharmacological effects, in male and female mice. In order to calculate $50\%$ lethal dose $(LD_{50})$, approximate LD and target organs, test article was administered twice by oral gavage to male and female ICR mice at total 1000, 500 and 250mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing. As the results, we could not find any mortalities, clinical signs, changes in the body weight and gross findings. The results obtained in this study suggest that the Polycan is non-toxic in mice and is therefore likely to be safe for clinical use. The L050 and approximate $(LD_{50})$ in mice after single oral dose of Polycan were considered over 1000 mg/kg, respectively.

• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.226-226
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• 2004

Circling (cir) mouse is a spontaneous mutant in the inner ear that was first reported in Korea. The mutation is transmitted by an autosomal recessive gene with 100 %- penetrance.. Homozygous mice are characterized by head-tossing, bi-directional circling behavior and deafness. Histologicalexamination of the inner ear reveals abnormalities of the region around the organ of Corti, spiral ganglion neurons, and outer hair cells. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.1036-1043
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• 2006

The present study was conducted to investigate the effect of Gamisamul-tang (GSMT) on atopic dermatitis (AD). AD was induced in NC/Nga mutant mice by DNCB treatment. GSMT administration reduced levels of skin severity scores. Serum levels of IgE, IgG, IgM, and inflammatory cytokines including IL-4, IL-4 and 1L-13 were significantly decreased by GSMT treatment. Levels of mRNA's encoding IL-4, IL-6, IL-13, $TNF-{\alpha}$, and $interferon-{\gamma}$ in the dermal tissue and draining lymph node (DLN) by real time RT-PCR analysis showed decrease by GSMT testament. Moreover, the number of CD4+ and CD8+ cells was significantly decreased in the spleen and DLN tissues. Histological examination showed that infiltration levels of immune cells in ear, skin, and DLN of AD-induced NC/Nga mice were much improved by GSMT treatment. The present data suggest that GSMT may play an important role in recovering AD symptoms by regulating immune reactivity.

• Development and Reproduction
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• v.16 no.4
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• pp.363-370
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• 2012

The outer dense fiber 2 (ODF2) protein is an important component of sperm tail outer dense fiber and localizes at the centrosome. It has been reported that the RO072 ES cell derived homozygote knock out of ODF2 results in an embryonic lethal phenotype, and XL169 ES cell derived heterozygote knock out causes severe defects in sperm tail development. The ODF2s splicing variant, Cenexin1, possesses a C-terminal extension, and the phosphorylation of serine 796 residue in an extended C-terminal is responsible for Plk1 binding. Cenexin1 assembles ninein and causes ciliogenesis in early stages of the cell cycle in a Plk1-independent manner. Alternatively, in the late stages of the cell cycle, G2/M phase, Cenexin1 binds to Plk1 and results in proper mitotic progression. In this study, to identify the in vivo function of Plk1 binding to phosphorylated Cenexin1 S796 residue, and to understand the in vivo functional differences between ODF2 and Cenexin1, we generated ODF2/Cenexin1 S796A/Cenexin1 WT expressing transgenic mice in a RO072 ES cell derived $ODF2^{+/-}$ knock out background. We observed a severe defect of sperm tail development by ectopic expression of Cenexin1 S796A mutant and no phenotypic differences between the ectopic expression of ODF2/Cenexin1 WT in $ODF2^{+/-}$ background and in normal wild type mice.

• BMB Reports
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• v.41 no.9
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• pp.651-656
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• 2008

A mouse with cataract, Kec, was generated from N-ethyl-N-nitrosourea (ENU) mutagenesis. Cataract in the Kec mouse was observable at about 5 weeks after birth and this gradually progressed to become completely opaque by 12 weeks. Dissection microscopy revealed that vacuoles with a radial or irregular shape were located primarily in the cortex of the posterior and equatorial regions of the lens. At the late stage, the lens structure was distorted, but not ruptured. This cataract phenotype was inherited in an autosomal recessive manner. We performed a genetic linkage analysis using 133 mutant and 67 normal mice produced by mating Kec mutant (BALB/c) and F1 (C57BL/6 $\times$ Kec) mice. The Kec locus was mapped to the 3 cM region encompassed by D14Mit34 and D14Mit69. In addition we excluded coding sequences of 9 genes including Rcbtb2, P2ry5, Itm2b, Med4, Nudt15, Esd, Lcp1, Slc25a30, and 2810032E02Rik as the candidate gene that causes cataract in the Kec mouse.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.143-148
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• 2014

Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7149-7152
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• 2014

A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or $Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

• Molecules and Cells
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• v.45 no.4
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• pp.180-192
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• 2022

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

• BMB Reports
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• v.47 no.2
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• pp.80-85
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• 2014

Altered acetylcholine (Ach) homeostasis is associated with loss of viability in flies, developmental defects in mice, and cognitive deficits in human. Here, we assessed the importance of Ach in Caenorhabditis elegans development, focusing on the role of Ach during dauer formation. We found that dauer formation was disturbed in choline acetyltransferase (cha-1) and acetylcholinesterase (ace) mutants defective in Ach biosynthesis and degradation, respectively. When examined the potential role of G-proteins in dauer formation, goa-1 and egl-30 mutant worms, expressing mutated versions of mammalian $G_o$ and $G_q$ homolog, respectively, showed some abnormalities in dauer formation. Using quantitative mass spectrometry, we also found that dauer larvae had lower Ach content than did reproductively grown larvae. In addition, a proteomic analysis of acetylcholinesterase mutant worms, which have excessive levels of Ach, showed differential expression of metabolic genes. Collectively, these results indicate that alterations in Ach release may influence dauer formation in C. elegans.

• Molecules and Cells
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• v.37 no.1
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• pp.59-65
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• 2014

Eph receptors and their ligands ephrins have been implicated in guiding the directed migration of neural crest cells (NCCs). In this study, we found that Wnt1-Cre-mediated expression of ephrinA5-Fc along the dorsal midline of the dien- and mesencephalon resulted in severe craniofacial malformation of mouse embryo. Interestingly, expression of cephalic NCC markers decreased significantly in the frontonasal process and branchial arches 1 and 2, which are target areas for the migratory cephalic NCCs originating in the dien- and mesencephalon. In addition, these craniofacial tissues were much smaller in mutant embryos expressing ephrinA5-Fc. Importantly, EphA7-positive cephalic NCCs were absent along the dorsal dien- and mesencephalon of mutant embryos expressing ephrinA5-Fc, suggesting that the generation of cephalic NCCs is disrupted due to ephrinA5-Fc expression. NCC explant experiments suggested that ephrinA5-Fc perturbed survival of cephalic NCC precursors in the dorsal midline tissue rather than affecting their migratory capacity, which was consistent with our previous report that expression of ephrinA5-Fc in the dorsal midline is responsible for severe neuroepithelial cell apoptotic death. Taken together, our findings strongly suggest that expression of ephrinA5-Fc decreases a population of cephalic NCC precursors in the dorsal midline of the dien- and mesencephalon, thereby disrupting craniofacial development in the mouse embryos.