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        검색결과 5

        1.
        2011.10 구독 인증기관·개인회원 무료
        The circling (cir/cir ) mouse is a murine model for human non‐syndromic deafness DFNB6. The causative gene is transmembrane inner ear (tmie), in which the mutation is a 40‐kilobase genomic deletion including tmie. The function of Tmie is unknown. To better understand the function of Tmie, we observed the spatiotemporal expression of tmie in the mouse cochlea using a Tmie‐specific antibody during postnatal inner ear development. Tmie was expressed in the cochlear hair cells of the mouse inner ear from embryonic days to adult. It is postulated that Tmie protein is involved in the hair cell structural formation and maturation before hearing onset (around P14), and maintenance of organ of Corti tissues after that. The cochlear hair cells of the circling mouse showed a basal‐to‐apical gradient of outer hair cell degeneration. The hair cell stereocilia bundles revealed the abnormal structure and it expanded to the apical region. In order to find the exact localization of Tmie protein inside the cell, we transfected the plasmids expressing GFP‐Tmie fusion protein into the HEI‐OC1 auditory hair cells. Tmie protein was colocalized with Calnexin (Canx), ER marker protein, but not with beta‐COP, Golgi marker protein. We next produced the Myo7a promoterdirected tmie expression transgenic mice to induce the phenotypic rescue of circling mice in a gene therapeutic way. Some circling mice with tmie transgene showed the normal behavior and hearing ability. These results indicate that tmie has a critical role in the inner ear development and hearing ability in the mice.
        2.
        2010.12 구독 인증기관 무료, 개인회원 유료
        The epigenetic therapy of cancers is emerging as an effective and valuable approach to both chemotherapy and the chemoprevention of cancer. The utilization of epigenetic targets that include histone methyltransferase (HMTase), Histone deacetylatase, and DNA methyltransferase, are emerging as key therapeutic targets. SET containing proteins such as the HMTase Setd1b has been found significantly amplified in cancerous cells. In order to shed some light on the histone methyl transferase family, we cloned the Setd1b gene from Mus musculus and build a collection of vectors for recombinant protein expression in E.coli that will pave the way for further structural biology studies. We prospect the role of the Setd1b pathway in cancer therapy and detail its unique value for designing novel anti-cancer epigenetic-drugs.
        4,000원
        3.
        2008.09 구독 인증기관 무료, 개인회원 유료
        Niemann-Pick type C disease (NPC), known an autosomal recessive disorder, is characterized by abnormal accumulation of cholesterol and glycolipid in late endosome/lysosome. The 95% case in NPC patients are caused by mutation of NPC1 gene, whose gene product is 13 transmembrane-domains and a sterol-sensing domain. The compensation of NPC1 by transgene expression in NPC1-deficient mouse recovered life span and sterility, but neurological correction incompletely, suggesting a possibility of gene therapy. Thus, in order to develop virial expression system for gene therapy of NPC, we isolated NPC1 cDNA and constructed Sindbis viral expression system for verification. NPC1 expression by Sindbis viral expression reduced the accumulation of cholesterol induced by treatment of U18666A and progesterone in both baby hamster kidney (BHK) cells and cultured hippocampal neurons. In addition, NPC1 expression increased the immunoreactivities of post-synaptic density protein 95kDa (PSD-95) in dendrites. On the basis of these results, we constructed a lentiviral vector for NPC1 expression and examined its expression in hippocampal cultured neurons.
        4,000원
        5.
        2012.09 KCI 등재 서비스 종료(열람 제한)
        Therapeutic cancer is a long lasting and turbulent history accompany with the milestones in surgical intervention, chemotherapy and radiotherapy. In the past decade, however, metastatic cancer still obstinately exists challenging the professional scientist. Beside the major forms of cancer treatment, Diphtheria toxin (DT) which is produced by a pathogenic strain of bacterium Corynebacterium diphtheria to shield themselves against the other dangerous organism, have been researched as a potential candidate to overcome the drawback such as non-specific, non-effect to drug resistant cancer cell and side effects when using chemotherapy and radiotherapy. In the context of suicide gene therapy, the DT expression under controlling of tissue-specific promoter will be targeted in cancer cell but defect in normal cell. The molecular mechanism, characteristic of DT-bases therapy and prominent achievements of preclinical and clinical studies for the past decade are summarized and discussed in this review.