簡易檢索 / 詳目顯示

研究生: 陳建瑩
Chen, Chien-Ying
論文名稱: 應用CRISPR/Cas9技術造成白花蝴蝶蘭DELLA基因的突變
Application of CRISPR/Cas9 technology to cause DELLA gene mutation in Phalaenopsis
指導教授: 張清俊
Chang, Ching-Chun
學位類別: 碩士
Master
系所名稱: 生物科學與科技學院 - 生物科技與產業科學系
Department of Biotechnology and Bioindustry Sciences
論文出版年: 2018
畢業學年度: 106
語文別: 中文
論文頁數: 92
中文關鍵詞: 台灣白花蝴蝶蘭(Phalaenopsis aphrodite subsp. formosana)GibberellinDELLACRISPR/Cas9
外文關鍵詞: Phalaenopsis aphrodite subsp. formosana, Gibberellin, DELLA, CRISPR/Cas9
相關次數: 點閱:90下載:4
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 台灣白花蝴蝶蘭(Phalaenopsis aphrodite subsp. formosana)為台灣原生種蝴蝶蘭,亦是商業化育種常使用的親本。但是栽培蝴蝶蘭的生長發育過於冗長,自播種至開花可能需要2至3年栽培。為了解決栽培時間冗長的問題參閱其他文獻研究,發現在植物激素中吉貝素(Gibberellin, GA)參與的生理調控作用如,種子發芽、生長以及開花作用等正向調節。但也在後續研究中發現當 GA 訊息傳導過程中 DELLA 蛋白會扮演負調控的角色,促使 GA 無法正常傳遞導致植物的生長調控受到限制,並且在阿拉伯芥實驗中將 DELLA 蛋白過量表現會造成植物產生侏儒的外表性狀以及對於生理調控都會受到相對應的限制。因此本實驗透過中研院蘭花網站比對阿拉伯芥 DELLA 基因找出白花蝴蝶蘭之中4個 DELLA 基因,接著利用CRISPR/Cas9基因編輯技術以及農桿菌轉殖來剔除剔除白花蝴蝶蘭之中3個 DELLA 基因,結果顯示在 T0代中疑似具有1個 DELLA 基因的序列有變異,但是對於白花蝴蝶蘭的生長與發育仍然有待進一步研究。

    Phalaenopsis aphrodite subsp. formosana is an endemic species in Taiwan and commonly used parental strains in breeding programs. However, the slow growth of Phalaenopsis, may take 2 to 3 years to develop from germination to flowering. Gibberellins (GA) have diverse functions in the regulation of plant growth and development such as seed germination, stem elongation and flowering. The DELLA proteins are the repressor in GA signaling transduction pathway. In Arabidopsis, overexpression of the DELLA protein could cause the semi-dwarf phenotype. In this study, three DELLA genes were identified by Blast the corresponding Arabidopsis orthologue genes against Orchidstra database. Subsequently, the CRISPR/Cas9 editing system was applied to knock out the DELLA genes in moth orchid through Agrobacteria-mediated transformation. The results showed that one of DELLA genes maybe mutated in T0 generation of transgenic moth orchid. The effects of growth and development in moth orchid resulting from the mutated DELLA gene need further to be analyzed in T1 generation.

    中文摘要 I 英文摘要 II 誌謝 VI 目錄 VII 表目錄 XI 圖目錄 XII 附錄圖目錄 XIII 縮寫表 XIV 一、研究計畫 1 1-1台灣白花蝴蝶蘭(Phalaenopsis aphrodite subsp. formosana) 1 1-2植物激素調節作用 1 1-3Gibberellin 在植物中生理功能 2 1-4Gibberellin 生合成路徑 4 1-5Gibberellin 訊息傳遞路徑 6 1-6DELLA 蛋白質的結構與功能 7 1-7DELLA 與 Gibberellin 相互調控關係 9 1-8植物基因改造技術之發展與應用 11 1-9基因專一性修飾技術 12 1-10鋅指核酸酶(Zinc finger nuclease; ZFN) 13 1-11轉錄類活化效應核酸酶(TALENs) 14 1-12成簇間隔之短迴文重複(CRISPR/Cas9) 16 1-13 CRISPR/Cas9技術於植物上之應用 17 1-14研究目的 18 二、材料與方法 19 2-1實驗材料 19 2-2植物基因轉殖之載體構築 19 2-3構築蝴蝶蘭之 CRISPR/Cas9-gRNA 載體 20 2-4構築表現載體所需使用之方法 24 2-5利用農桿菌感染蘭花 30 2-6蘭花無菌播種 30 2-7篩選建立轉殖白花蝴蝶蘭植株 31 2-8萃取植物 DNA Cetylrimethylammonium bromide(CTAB) 31 2-9利用 PCR 偵測外源基因存在於轉殖白花蝴蝶蘭基因組 33 2-10配置15% Native PAGE 膠體 33 2-11利用 Native PAGE 進行 Genotyping 分析 34 2-12構築 TA 表現載體 34 三、結果 35 3-1分析白花蝴蝶蘭的 DELLA 基因分析 35 3-2生物資訊分析白花蝴蝶蘭組織中 DELLA 基因的表現強度 36 3-3構築 Cas9/gRNA 表現載體 37 3-4白花蝴蝶蘭轉殖以及篩選 38 3-5利用 PCR 偵測外源基因之存在 38 3-6分析白花蝴蝶蘭 DELLA 基因剔除情況 39 3-7定序分析白花蝴蝶蘭轉殖品系之 DELLA 目標片段 39 3-8克隆入TA 載體進行定序分析 DELLA 目標片段 40 3-9總結 40 四、討論 42 4-1轉殖植物的篩選 42 4-2CRISPR/Cas9表現載體剪切效率 42 4-3應用 CRISPR/Cas9編輯蘭科植物 43 4-4白花蝴蝶蘭 DELLA 基因的演化關係 44 參考文獻 45 圖表 54 附錄 85

    吳佩諭,轉殖似轉錄激活因子蛋白核酸酶(TALEN)來改變菸草葉綠體 DNA 序列之研究,國立成功大學生物科技研究所碩士論文,2017。

    林讚標,台灣蘭科植物2,南天書局,台灣,167-174,1988。

    陳怡寬,利用細胞穿透胜肽運送 DNA 進入葉綠體,國立成功大學生物科技研究所碩士論文,2014。

    陳謫凡,台灣原生種白花蝴蝶蘭細胞分裂氧化酶基因之研究,國立成功大學生物科技研究所碩士論文,2017。

    黃品升,利用職務熱休克蛋白 HSP 101 來提升外源蛋白質轉譯能疫能力之研究,國立成功大學生物科技研究所碩士論文,2007。

    蘇源霖,利用似轉錄激活因子蛋白核酸酶(TALEN)技術對植物粒腺體 nad1 基因進行編輯,國立成功大學生物科技研究所碩士論文,2016。

    Becker, H. and Léon, J. Stability analysis in plant breeding. Plant Breeding 101, 1-23, 1988.

    Bewleyl, J. D. Seed germination and dormancy. The Plant Cell 9, 1055-1066, 1997.

    Bi, H. and Yang, B. Gene editing with TALEN and CRISPR/Cas9 in rice. Progress in Molecular Biology and Translational Science 124, 4154-4161, 2014.

    Boch, J. TALEs of genome targeting. Nature Biotechnology 29, 135-136, 2011.

    Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T., Nickstadt, A. and Bonas, U. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509-1512, 2009.

    Bogdanove, A. J., Schornack, S. and Lahaye, T. TAL effectors: finding plant genes for disease and defense. Plant Biology 13, 394-401, 2010.

    Boss, P. K. and Thomas, M. R. Association of dwarfism and floral induction with a grape 'green revolution' mutation. Nature 416, 847-850, 2002.

    Boss, P. K., Buckeridge, E. J., Poole, D. and Thomas, A. M. New insights into grapevine flowering. Plant Biology 30, 593-606, 2003.

    Brodersen, P. and Voinnet, O. The diversity of RNA silencing pathways in plants. Trends in Genetics 22, 268-280, 2006.

    Capecchi, M. R. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nature 6, 507-512, 2005.

    Chen, K., Shan, Q. and Gao, C. An efficient TALEN mutagenesis system in rice. PLoS One 69, e2-e8, 2014.

    Chen, W. S., Liu, H. Y., Liu, Z. H., Yang, L. and Chen, W. H. gibberellin and temperature influence carbohydrate content and flowering in Phalaenopsis. Physiologia Plantarum 90, 391-395, 1994.

    Cheng, H., Qin, L., Lee, S., Fu, X., Richards, D. E., Cao, D., Luo, D., Harberd, N. P. and Peng, J. Gibberellin regulates Arabidopsis floral development via suppression of DELLA protein function. Plant Cell 131, 1055-1064, 2004.

    Chong, R., Xianju, L., Zhan, Z., Yi, W., Wei, D., Shaohua, L. and Zhenchang, L. CRISPR/Cas9-mediated efficient targeted mutagenesis in Chardonnay (Vitis vinifera L). Scientific Reports 6, 32289, 2016.

    Curtin, S. J., Zhang, F., Sander, J. D., Haun, W. J., Starker, C., Baltes, N. J., Reyon, D., Dahlborg, E. J., Goodwin, M. J. and Coffman, A. P. Targeted mutagenesis of duplicated genes in soybean with zinc-finger nucleases. Plant Physiology 156, 466-473, 2011.

    Davidson, S. E., Elliott, R. C., Helliwell, C. A., Poole, A. T. and Reid, J. B. The pea gene NA encodes ent-kaurenoic acid oxidase. Plant Physiology 131, 335-344, 2003.

    Davidson, S. E., Elliott, R. C., Helliwell, C. A., Poole, A. T. and Reid, J. B. The pea gene LH encodes ent-kaurene oxidase. Plant Physiology 134, 1123-1134, 2004.

    Dill, A. and Sun, T. Synergistic derepression of gibberellin signaling by removing RGA and GAI function in Arabidopsis thaliana. Genetics 159, 777-785, 2001.

    Dill, A., Jung, H. S. and Sun, T. P. The DELLA motif is essential for gibberellin-induced degradation of RGA. Proceedings of the National Academy of Sciences of the United States of America 98, 14162-14167, 2001.

    Eriksson, S., Bohlenius, H., Moritz, T. and Nilsson, O. GA4 is the active gibberellin in the regulation of LEAFY transcription and Arabidopsis floral initiation. Plant Cell 18, 2172-2181, 2006.

    Feng, Z. Efficient genome editing in plants using a CRISPR/Cas system. Cell Research 23, 1229-1232, 2013.

    Fyodor, D., Urnov, E. J., Rebar, M. C., Holmes, H., Zhang, C. and Philip, D. Genome editing with engineered zinc finger nucleases. Nature 11, 636-646, 2010.

    Garcia-Martinez, J. L., Lopez-Diaz, I., Sanchez-Beltran, M. J., Phillips, A. L., Ward, D. A., Gaskin, P. and Hedden, P. Isolation and transcript analysis of gibberellin 20-oxidase genes in pea and bean in relation to fruit development. Plant Molecular Biology 33, 1073-1084, 1997.

    Griffiths, J., Murase, K., Rieu, I., Zentella, R., Zhang, Z. L., Powers, S. J., Gong, F., Phillips, A. L., Hedden, P., Sun, T. P., and Thomas, S. G. Genetic characterization and functional analysis of the GID1 gibberellin receptors in Arabidopsis. Plant Cell 18, 3399-3414, 2006.

    Gupta, R. M. and Musunuru, K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. The Journal of Clinical Investigation 293, 4154-4161, 2014.

    Hedden, P. and Thomas, S. G. Gibberellin biosynthesisandits regulation. Biochemical Journal 444, 11-25, 2012.

    Helliwell, C. A., Sullivan, J. A. and Muld, R. M. A plastid envelope location of Arabidopsis ent-kaurene oxidase links the plastid and endoplasmic reticulum steps of the gibberellin biosynthesis pathway. Plant Journal 28, 201-208, 2001.

    Hironori, I., Miyako, T., Hiroshi, K., Xinbo, C., Yuji, K. and Makoto, M. The gene encoding tobacco gibberellin 3 β-hydroxylase is expressed at the site of GA action during stem elongation and flower organ development. The Plant Journal 20,115-124, 1999.

    Hua, K., Tao, X. and Zhu, J. K. Expanding the base editing scope in rice by using Cas9 variants. Plant Biotechnology Journal 125, 11-17, 2018.

    Huizen, R., Ozga, J. A. and Reinecke, D. M. Seed and hormonal regulation of Gibberellin 20-oxidase expression in pea pericarp. Plant Physiology 115, 123-128, 1997.

    Hwang, W. Y. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nature Biotechnology 31, 227-229, 2013.

    Itoh, H., Sasaki, A., Ueguchi-Tanaka, M., Ishiyama, K., Kobayashi, M., Hasegawa, Y., Minami, E., Ashikari, M. and Matsuoka, M. Dissection of the phosphorylation of rice DELLA protein, slender rice1. Plant and Cell Physiology 46, 1392-1399, 2005.

    Jayne, G., Kohji, M., Ivo, R., Rodolfo, Z., Zhong, Z., Stephen, J., Powers, F. G. and Andrew L. Genetic characterization and functional analysis of the gid1 gibberellin receptors in Arabidopsis. The Plant Cell 18, 3399-3414, 2016.

    Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A. and Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816-821, 2012.

    John, G. D., Ella, H., Daniel, B., Zuzana, T., Mudra, H., Ian S., Meagan, S., Benjamin, L., E., Ramnik, J. X. and David, E. R. Rational design of highly active sgRNAs for CRISPR-Cas9–mediated gene inactivation. Nature Biotechnology 24, 1262-1267, 2014.

    Kende, H. and Zeevaart, J. The five “classical” plant hormones. Plant Cell 9, 1197-1210, 1997.

    Kim, J. S. and Pabo, C. O. Getting a handhold on DNA: design of poly-zinc finger proteins with femtomolar dissociation constants. Sciences 95, 2812-2817, 1998.

    Kodym, A. and Afza, R. Physical and chemical mutagenesis. Plant Functional Genomics 38, 189-203, 2003.

    Lawit, S. J., Wych, H. M., Xu, D., Kundu, S. and Tomes, D. T. Maize DELLA proteins dwarf plant8 and dwarf plant9 as modulators of plant development. Plant Cell Physiology 51, 1854-1868, 2010.

    Lewis, N. M. The chemistry of gibberellins: An Overview. Chemical review 92, 573-612, 1992.

    Li, J. F., Zhang, D. and Sheen, J. Cas9-based genome editing in Arabidopsis and tobacco. Methods in Enzymology 546, 459-472, 2014.

    Ling, K., Haitao, C., Weixiong, Z., Simei, H., Zijun, X., Yesheng, Z., Liang, Y., Chaofang, Z., Fengmei, H., Junwen, C., Peng, Z., Guanghui, Z, Shengchao, Y., Yang, D., Wen, W. and Jing, C. Building a genetic manipulation tool box for orchid biology: identification of constitutive promoters and application of CRUSPR/Cas9 in the orchid, dendrobium officinale. Plant Science 10, 333-389, 2017.

    Liu, P. Q., Rebar, E. J., Zhang, L., Liu, Q., Jamieson, A. C., Liang, Y., Qi, H., Li, P. X., Chen, B. and Mendel, M. C. Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. The Journal of Biological Chemistry 276, 11323-11334, 2001.

    Mao, Y. Application of the CRISPR-Cas system for efficient genome engineering in plants. Molecular Plant 6, 2008-2011, 2013.

    McGinnis, K., Murphy, N., Carlson, A. R., Akula, A., Akula, C., Basinger, H., Carlson, M., Hermanson, P., Kovacevic, N. and McGill, M. A. Assessing the efficiency of RNA interference for maize functional genomics. Plant Physiology 143, 1441-1451, 2007.

    McManus, M. T. and Sharp, P. A. Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics 3, 737-747, 2002.
    Mehta, A. and Haber, J. E. Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harbor Perspectives Biology 7, 6-9, 2014.

    Miller, J. C., Holmes, M. C., Wang, J., Guschin, D. Y., Lee, Y. L., Rupniewski, I., Beausejour, C. M., Waite, A. J., Wang, N. S. and Kim, K. A. An improved zinc-finger nuclease architecture for highly specific genome editing. Nature Biotechnology 25, 778-785, 2007.

    Miller, J. C., Tan, S., Qiao, G., Barlow, K. A., Wang, J., Xia, D. F., Meng, X., Paschon, D. E., Leung, E. and Hinkley, S. J. A TALE nuclease architecture for efficient genome editing. Nature Biotechnology 29, 143-148, 2011.

    Mitchum, M. G., Yamaguchi, S., Hanada, A., Kuwahara, A., Yoshioka, Y., Kato, T., Tabata, S., Kamiya, Y. and Sun, T. P. Distinct and overlapping roles of two gibberellin 3-oxidases in Arabidopsis development. The Plant Journal 45, 804-818, 2006.

    Nakajima, M., Takita, K., Wada, H., Mihara, K., Hasegawa, M., Yamaguchi, I., and Murofushi, N. Partial purification and characterization of a gibberellin binding protein from seedlings of Azukia angularis. The Plant Journal 241, 782-786, 1997.

    Nakayama, M. and Ohara, O. Improvement of recombination efficiency by mutation of red proteins. Future Science 38, 917-924, 2005.

    Nishimasu, H., Ran, F., Hsu, P. D., Konermann, S., Shehata, S., Dohmae, N., Ishitani, R., Zhang, F. and Nureki, O. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156, 935-949, 2001.

    Osakabe, K., Osakabe, Y. and Toki, S. Site-directed mutagenesis in Arabidopsis using custom-designed zinc finger nucleases. Proceedings of the National Academy of Sciences of the United States of America 107, 12034-12039, 2010.

    Pabo, C. O., Peisach, E. and Grant, R. A. Design and selection of novel Cys2His2 zinc finger proteins. Annual Review of Biochemistry 70, 313-340, 2001.

    Parinov, S., Sevugan, M., Ye, D., Yang, W. C., Kumaran, M. and Sundaresan, V. Analysis of flanking sequences from dissociation insertion lines: a database for reverse genetics in Arabidopsis. Plant Cell 11, 2263-2270, 1999.

    Patrick, A., Alan, H., David, C., Baulcombe, D. and Nicholas P. H. Modulation of floral development by a gibberellin-regulated microRNA. Development 131, 3357-3365, 2004.

    Pellicer, A., Robins, D., Wold, B., Sweet, R., Jackson, J., Lowy, I., Roberts, J. M., Sim, G. K., Silverstein, S. and Axel, R. Altering genotype and phenotype by DNA-mediated gene transfer. Science 209, 1414-1422, 1980.

    Peng, J., Richards, D. E., Hartley, N. M., Murphy, G. P., Devos, K. M., Flintham, J. E., Beales, J., Fish, L. J., Worland, A. J., Pelica, F., Sudhakar, D., Christou, P., Snape, J. W., Gale, M. D. and Harberd, N. P. 'Green revolution' genes encode mutant gibberellin response modulators. Nature 400, 256-261, 1999.

    Phinney, B. O. Growth response of single-gene dwarf mutation in maize to gibberellin acid. Proceedings of the National Academy of Sciences of the United States of America 42, 185-189, 1956.

    Shewmaker, K. and Stalker, D. Modifying starch biosynthesis with transgenes in potatoes. Plant Physiology 100, 1083-1086, 1992.

    Shukla, V. K., Doyon, Y., Miller, J. C., DeKelver, R. C., Moehle, E. A., Worden, S. E., Mitchell, J. C., Arnold, N. L., Gopalan, S. and Meng, X. Precise genome modification in the crop species Zea mays using zinc-finger nucleases. Nature 459, 437-441, 2009.

    Silverstone, A. L., Ciampaglio, C. N. and Sun, T. The Arabidopsis RGA gene encodes a transcriptional regulator repressing the gibberellin signal transduction pathway. Plant Cell 10, 155-169, 1998.

    Singer, B. and Kusmierek, T. K. Chemical mutagenesis. Biochemistry 51, 655-693, 1982.

    Sun, T. P. and Gubler, F. Molecular mechanism of gibberellin signaling in plants. Annual Review Plant Biology 55, 197-223, 2004.

    Sundaresan, V., Springer, P., Volpe, T., Haward, S., Jones, J. D., Dean, C., Ma, H. and Martienssen, R. Patterns of gene action in plant development revealed by enhancer trap and gene trap transposable elements. Genes 9, 1797-1810, 1995.

    Tauer, J. E. International protection of genetic information: the progression of the human genome project and the current framework of human rights doctrines. Denver Journal of International Law and Policy 29, 209-237, 2001.

    Terezie, U. and Gerhard, L. M. Gibberellins and seed germination. Annual Plant Reviews 49, 253-284, 2016.

    Tesson, L., Usal, C., Menoret, S., Leung, E., Niles, B. J., Remy, S., Santiago, Y., Vincent, A. I., Meng, X. and Zhang, L. Knockout rats generated by embryo microinjection of TALENs. Nature Biotechnology 29, 695-696, 2011.

    Thomas, S. G. and Sun, T. P. Update on gibberellin signaling. A tale of the tall and the short. Plant Physiology 135, 668-676, 2004.

    Tsay, H. S., Ho, H. M., Gupta, S. K., Wang, C. S., Chen, P. T. and Chen, E. C. Development of pollen mediated activation tagging system for Phalaenopsis and Doritaenopsis. Electronic Journal of Biotechnology 15, 9-19, 2012.

    Tudzynski, B. Mihlan, M. and Rojas, C. Characterization of the final two genes of the gibberellin biosynthesis gene cluster. Biological Chemistry 278, 28635-28643, 2003.

    Tyler, L., Thomas, S. G., Hu, J., Dill, A., Alonso, J. M., Ecker, J. R. and Sun, T. P. DELLA proteins and gibberellin-regulated seed germination and floral development in Arabidopsis Plant Physiology 135, 1008-1019, 2004.

    Wang, F. and Deng, X. W. Plant ubiquitin-proteasome pathway and its role in gibberellin signaling. Cell 21, 1286-2194, 2011.

    Wang, H., Pan, J., Li, Y., Lou, D., Hu, Y. and Yu, D. The DELLA-CONSTANS transcription factor cascade integrates gibberellic acid and photoperiod signaling to regulate flowering. Plant Physiology 10, 479-488, 2016.

    Wen, W., Deng, Q., Jia, H., Wei, L., Wei, J., Wan, H., Yang, L., Cao, W. and Ma, Z. Sequence variations of the partially dominant DELLA gene Rht-B1c in wheat and their functional impacts. Journal of Experimental Botany 64, 299-312, 2013.

    Xu, Y. L., Gage, D. A. and Zeevaart, J. A. Gibberellins and stem growth in Arabidopsis thaliana effects of photoperiod on expression of the GA4 and GA5. Plant Physiology 114, 1471-1476, 1997.

    Ye, S., Cole-Strauss, A. C., Frank, B. and Kmiec, E. B. Targeted gene correction: a new strategy for molecular medicine. Molecular Medicine Today 4, 431-437, 1998.

    Zentella, R., Zhang, Z. L., Park, M., Thomas, S. G., Endo, A., Murase, K., Fleet, C. M., Jikumaru, Y., Nambara, E., Kamiya, Y. and Sun, T. P. Global analysis of della direct targets in early gibberellin signaling in Arabidopsis. Plant Cell 19, 3037-3057, 2007.

    Zhang, H., Zhang, J., Wei, P., Zhang, B., Gou, F. and Feng, Z. The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation. Plant Biotechnology 12, 797-807, 2014.

    Zhang, Y., Zhang, F., Li, X., Baller, J. A., Qi, Y., Starker, C. G., Bogdanove, A. J. and Voytas, D. F. Transcription activator-like effector nucleases enable efficient plant genome engineering. Plant Physiology 161, 20-27, 2013.

    Zou, Q., Gang, K., Yang, Q., Liu, X., Tang, X., Lu, H., He, J. and Luo, L. The CCCH-type zinc finger transcription factor Zc3h8 represses NF-κB-mediated inflammation in digestive organs in zebrafish. The Journal of Biological Chemistry 293, 11971-11983, 2018.

    下載圖示 校內:2023-09-10公開
    校外:2023-09-10公開
    QR CODE