• Title/Summary/Keyword: transgenic mice

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Novel Disease Model of Chronic Neutrophilic Leukemia

  • Seo, Byoung-Boo;Min, Sung-Hun;Lee, Eun-Ji;Ryoo, Zae-Young;Park, Hum-Dai
    • Reproductive and Developmental Biology
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    • v.35 no.4
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    • pp.421-425
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    • 2011
  • The experimental manipulation of protooncogenes and their gene products is a valuable research tool for the study of human neoplasia. In this study, the recently identified human cervical cancer protooncogene (HccR-2) was expressed in transgenic mice under the control of the tetracycline regulatory system. The phenotype observed was similar in many respects to human chronic neutrophilic leukemia (CNL). Thus, the HccR-2 transgenic mouse model is important not only for investigating the biological properties of the HccR-2 protooncogene in vivo, but also for analyzing the mechanisms involved in the progression of CNL.

Different expression of human GFAP promoter-derived GFP in different subsets of astrocytes in the mouse brain

  • Moon, Young-Hye;Kim, Hyun-Jung;Kim, Joo-Yeon;Kim, Hyun;Kim, Woon-Ryoung;Sun, Woong
    • Animal cells and systems
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    • v.15 no.4
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    • pp.268-273
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    • 2011
  • Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.

Human Keratin 14 Driven HPV 16 E6/E7 Transgenic Mice Exhibit Hyperkeratinosis

  • Kim, Sung-Hyun;Kim, Kil-Soo;Lee, Eun-Ju;Kim, Myoung-Ok;Park, Jun-Hong;Cho, Kyoung-In;Kazuhiko-Imakawa;Hyun, Byung-Hwa;Chang, Kyu-Tae;Lee, Hoon-Taek;Ryoo, Zae-Young
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.215-215
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    • 2004
  • Human papillomavirus type 16 (HPV16) has been known as a major causative factor for the development of uterine cervical carcinomas. To investigate the in vivo activity of HPV16 expressed in squamous epithelia, transgenic mice harboring HPV16 E6/E7 with human keratin 14 (hK14) promoter were generated. Grossly, hK14 driven HPV16 E6/E7 transgenic mice exhibited multiple phenotypes, including wrinkled skin that was apparent prior to the appearance of hair in neonates, thickened ears, and loss of hair in adults. (omitted)

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Manipulation of Hepatitis B Viral DNA for Generating Transgenic Mice

  • Kim, Seung-Hee;Park, Sang-Ho;Kim, Tae-Gyun;Lee, Song-Deuk;Aree Moon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.178-178
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    • 1996
  • Hepatitis B virus (HBV) infection is one of the serious problems in Southeast Asia including Korea because it causes chronic hepatitis, which can easily be transformed In fatal conditions such as cirrhosis and hepatoma. Even though lots of informations on structural characteristics and gene expression mechanisms have been accumulated, the mechanism for HBV-induced hepatocellular injury which is believed to be the consequences of the immunological response is not well understood. In order tn perform immunopathological studies for prevention and treatment of HBV infection, we designed transgenic mice as a disease model which can mimic HBV infection, In this study, a promoter-HBV DNA fragment for the preparation of HBV transgenic mice has been constructed. To add a proper enzyme site on 5' end of HBV gene, total HBV (subtype adr) gene was inserted into BamHI site of pBluescript SK vector and reextracted by PstI-SacI treatment A liver-specific promoter, rat ${\alpha}$ 2u globulin gene promoter, was insrted to pBluescript SK vector and reextracted by BamHI-PstI treatment, Promoter-HBV DNA was constructed by ligation of two fragments using identical PstI sites. For large scale production of promoter-HBV DNA, it was inserted to BamHI-SacI site of pBluescript SK vector.

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Functional Genomics Approach Using Mice

  • Sung, Young-Hoon;Song, Jae-Whan;Lee, Han-Woong
    • BMB Reports
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    • v.37 no.1
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    • pp.122-132
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    • 2004
  • The rapid development and characterization of the mouse genome sequence, coupled with comparative sequence analysis of human, has been paralleled by a reinforced enthusiasm for mouse functional genomics. The way to uncover the in vivo function of genes is to analyze the phenotypes of the mutant animals. From this standpoint, the mouse is a suitable and valuable model organism in the studies of functional genomics. Therefore, there have been enormous efforts to enrich the list of the mutant mice. Such a trend emphasizes the random mutagenesis, including ENU mutagenesis and gene-trap mutagenesis, to obtain a large stock of mutant mice. However, since various mutant alleles are needed to precisely characterize the role of a gene in vivo, mutations should be designed. The simplicity and utility of transgenic technology can satisfy this demand. The combination of RNA interference with transgenic technology will provide more opportunities for researchers. Nevertheless, gene targeting can solely define the in vivo function of a gene without a doubt. Thus, transgenesis and gene targeting will be the major strategies in the field of functional genomics.

Tumorigenesis of Transgenic Mice Induced by Mouse Vasopressin-SV40 T Hybrid Oncogene

  • Lee, Eun-Ju;Kim, Myoung-Ok;Kim, Sung-Hyun;Park, Jun-Hong;Park, Jung-Ok;Cho, Kyong-In;Park, Hum-Dai;Ryoo, Zae-Young
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.92-92
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    • 2002
  • The neuropeptide vasopressin (VP) is a nine- amino acid hormone synthesized as preprohormone in the cell bodies of hypothalamic magnocellular neurons. The tumor in magnocellular neurons of the hypothalamus is associated with disfunctions of the cell bodies, leading to the diabetes insipidus. In order to produce the disease models with a defect in VP synthesis and its secretion, we have produced the transgenic mice regulated by VP constructs containing 3.8 kbp of the 5'flanking region and all the exons and introns in the mouse VP gene, which was fused at the end of exon 3 to a SV40 Tag. The two VP-transgene constructs differed by the lengths of their VP gene 3' flanking regions (2.1 versus 3.6 kbp). (omitted)

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Effect of Orally Administered Lactobacillus brevis HY7401 in a Food Allergy Mouse Model

  • Lee, Jeongmin;Bang, Jieun;Woo, Hee-Jong
    • Journal of Microbiology and Biotechnology
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    • v.23 no.11
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    • pp.1636-1640
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    • 2013
  • We had found that orally administered Lactobacillus species were effective immune modulators in ovalbumin (OVA)-sensitized mice. To validate these findings, we investigated the effects of orally administered Lactobacillus brevis HY7401 in OVA-T cell receptor transgenic mice. This strain showed a tendency to induce Th1 cytokines and inhibit Th2 cytokines. All assayed isotypes of OVA-specific antibody were effectively reduced. Systemic anaphylaxis was also relatively reduced with the probiotic administration. These results reveal that L. brevis HY7401 might be useful to promote anti-allergic processes through oral administration.

Neuroprotective Effect of Rapamycin (Autophagy Enhancer) in Transgenic SOD1-G93A Mice of Amyotrophic Lateral Sclerosis (근위축성측삭경화증의 SOD1-G93A 유전자 이식 마우스 모델에서 라파마이신의 신경보호효과)

  • Ahn, Suk-Won;Jeon, Gye Sun;Park, Kwang-Yeol;Hong, Yoon-Ho;Lee, Kwang-Woo;Sung, Jung-Joon
    • Annals of Clinical Neurophysiology
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    • v.15 no.2
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    • pp.53-58
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    • 2013
  • Background: The autophagy is the major route for lysosomal degradation of misfolded protein aggregates and oxidative cell components. We hypothesized that rapamycin (autophagy enhancer) would prolong the survival of motor neuron and suppress the disease progression in amyotrophic lateral sclerosis (ALS). Methods: A total of 24 transgenic mice harboring the human G93A mutated SOD1 gene were used. The clinical status involving rotarod test and survival, and biochemical study of ALS mice model were evaluated. Results: The onset of symptoms was significantly delayed in the rapamycin administration group compared with the control group. However, after the clinical symptom developed, the rapamycin exacerbated the disease progression and shortened the survival of ALS mice model, and apoptosis signals were up-regulated compared with control group. Conclusions: Even though further detailed studies on the relevancy between autophagy and ALS will be needed, our results revealed that the rapamycin administration was not effective for being novel promising therapeutic strategy in ALS transgenic mice and exacerbated the apoptosis.

The Effector Functions of Mature T Lymphocytes Are Impaired in Transgenic Mice Expressing the SH2 Domain of TSAd/Lad

  • Choi, Youngbong;Park, Eunkyung;Ahn, Eunseon;Park, Inyoung;Yun, Yungdae
    • Molecules and Cells
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    • v.28 no.3
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    • pp.183-188
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    • 2009
  • TSAd/Lad is a T cell adaptor molecule involved in $p56^{lck}$-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the $p56^{lck}$ proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as $Ca^{2+}$ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.

Expression of the Transgene is Consistently Inherited to High Numbers of Generations and Independent on Its Source

  • Zheng, Zhen-Yu;Oh, Keon-Bong;Koo, Deog-Bon;Han, Yong-Mahn;Lee, Kyung-Kwang
    • Reproductive and Developmental Biology
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    • v.32 no.1
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    • pp.39-43
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    • 2008
  • Most studies on transgenic bioreactors have focused on expression levels of interest genes. In this study we examined whether transgenic bioreactors would inherit expression level of the Oansgene to long-term generations independently of transgene sources. We employed three transgenic mice, which were separately reported, carrying different transgenes and copy numbers, 27 kb of hLF and 22 kb of hIL-10 genomic sequences, and 1.3 kb of hTPO cDNA, respectively. Three females of the transgenic lineages crossbred with a wild-type male up to 20 generations to test transgenic frequencies of their progenies and to determine expression levels of the transgenes. Ultimately, transmission rates of kLF, hIL-10, and hTPO were $64.3{\pm}7.0$, $59.3{\pm}9.8$, and $56.1{\pm}9.7$, respectively, appeared following Mendelian pattern of inheritance. Notably, we found that levels of expressions of hLF, hIL-10, and hTPO in milk were sustained to high numbers of generations. No transgene silencing of expression was observed in every generations of all transgenic mice. In conclusion, we suggest that once established animal bioreactors could consistently transmit the transgene to continual generations, without loss of expressional activity, independently of transgene sources.