請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50063完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林淑華(Shu-Wha Lin) | |
| dc.contributor.author | Shi-Feng Yang | en |
| dc.contributor.author | 楊士鋒 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:28:53Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-08 | |
| dc.identifier.citation | 1. Puente, X.S., et al., A genomic view of the complexity of mammalian proteolytic systems. Biochem Soc Trans, 2005. 33(Pt 2): p. 331-4.
2. Di Cera, E., Serine proteases. IUBMB Life, 2009. 61(5): p. 510-5. 3. Bugge, T.H., T.M. Antalis, and Q. Wu, Type II transmembrane serine proteases. J Biol Chem, 2009. 284(35): p. 23177-81. 4. Leytus, S.P., et al., A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. Biochemistry, 1988. 27(3): p. 1067-74. 5. Tsuji, A., et al., Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. J Biol Chem, 1991. 266(25): p. 16948-53. 6. Kawamura, S., et al., Complete nucleotide sequence, origin of isoform and functional characterization of the mouse hepsin gene. Eur J Biochem, 1999. 262(3): p. 755-64. 7. Vu, T.K., et al., Identification and cloning of the membrane-associated serine protease, hepsin, from mouse preimplantation embryos. J Biol Chem, 1997. 272(50): p. 31315-20. 8. Somoza, J.R., et al., The structure of the extracellular region of human hepsin reveals a serine protease domain and a novel scavenger receptor cysteine-rich (SRCR) domain. Structure, 2003. 11(9): p. 1123-31. 9. Herter, S., et al., Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. Biochem J, 2005. 390(Pt 1): p. 125-36. 10. Hedstrom, L., Serine protease mechanism and specificity. Chem Rev, 2002. 102(12): p. 4501-24. 11. Werb, Z., et al., Matrix-degrading proteases and angiogenesis during development and tumor formation. APMIS, 1999. 107(1): p. 11-8. 12. Kirchhofer, D., et al., Hepsin activates pro-hepatocyte growth factor and is inhibited by hepatocyte growth factor activator inhibitor-1B (HAI-1B) and HAI-2. FEBS Lett, 2005. 579(9): p. 1945-50. 13. Kazama, Y., et al., Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation. J Biol Chem, 1995. 270(1): p. 66-72. 14. Ustach, C.V., et al., A novel signaling axis of matriptase/PDGF-D/ss-PDGFR in human prostate cancer. Cancer Res, 2010. 70(23): p. 9631-40. 15. Shia, S., et al., Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B. J Mol Biol, 2005. 346(5): p. 1335-49. 16. Wu, Q., et al., Generation and characterization of mice deficient in hepsin, a hepatic transmembrane serine protease. J Clin Invest, 1998. 101(2): p. 321-6. 17. Yu, I.S., et al., Mice deficient in hepsin, a serine protease, exhibit normal embryogenesis and unchanged hepatocyte regeneration ability. Thromb Haemost, 2000. 84(5): p. 865-70. 18. Wu, Q. and G. Parry, Hepsin and prostate cancer. Front Biosci, 2007. 12: p. 5052-9. 19. Guipponi, M., et al., Mice deficient for the type II transmembrane serine protease, TMPRSS1/hepsin, exhibit profound hearing loss. Am J Pathol, 2007. 171(2): p. 608-16. 20. Brunati, M., et al., The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin. Elife, 2015. 4: p. e08887. 21. Tanimoto, H., et al., Hepsin, a cell surface serine protease identified in hepatoma cells, is overexpressed in ovarian cancer. Cancer Res, 1997. 57(14): p. 2884-7. 22. Zacharski, L.R., et al., Expression of the factor VII activating protease, hepsin, in situ in renal cell carcinoma. Thromb Haemost, 1998. 79(4): p. 876-7. 23. Dhanasekaran, S.M., et al., Delineation of prognostic biomarkers in prostate cancer. Nature, 2001. 412(6849): p. 822-6. 24. Magee, J.A., et al., Expression profiling reveals hepsin overexpression in prostate cancer. Cancer Res, 2001. 61(15): p. 5692-6. 25. Klezovitch, O., et al., Hepsin promotes prostate cancer progression and metastasis. Cancer Cell, 2004. 6(2): p. 185-95. 26. Xuan, J.A., et al., Antibodies neutralizing hepsin protease activity do not impact cell growth but inhibit invasion of prostate and ovarian tumor cells in culture. Cancer Res, 2006. 66(7): p. 3611-9. 27. Miao, J., et al., Hepsin colocalizes with desmosomes and induces progression of ovarian cancer in a mouse model. Int J Cancer, 2008. 123(9): p. 2041-7. 28. Tervonen, T.A., et al., Deregulated hepsin protease activity confers oncogenicity by concomitantly augmenting HGF/MET signalling and disrupting epithelial cohesion. Oncogene, 2016. 35(14): p. 1832-46. 29. Srikantan, V., et al., HEPSIN inhibits cell growth/invasion in prostate cancer cells. Cancer Res, 2002. 62(23): p. 6812-6. 30. Nakamura, K., et al., Hepsin shows inhibitory effects through apoptotic pathway on ovarian cancer cell lines. Int J Oncol, 2006. 28(2): p. 393-8. 31. Merrell, A.J. and G. Kardon, Development of the diaphragm -- a skeletal muscle essential for mammalian respiration. FEBS J, 2013. 280(17): p. 4026-35. 32. Agostoni, E., J.N. Davis, and E.J.M. Campbell, The respiratory muscles : mechanics and neural control. 2. ed. 1970, London,. 348 s. 33. Perry, S.F., et al., The evolutionary origin of the mammalian diaphragm. Respir Physiol Neurobiol, 2010. 171(1): p. 1-16. 34. Finsterer, J., Cardiopulmonary support in duchenne muscular dystrophy. Lung, 2006. 184(4): p. 205-15. 35. Pickering, M. and J.F. Jones, The diaphragm: two physiological muscles in one. J Anat, 2002. 201(4): p. 305-12. 36. Pearce, J.M., Henry Gray's Anatomy. Clin Anat, 2009. 22(3): p. 291-5. 37. Allan, D.W. and J.J. Greer, Embryogenesis of the phrenic nerve and diaphragm in the fetal rat. J Comp Neurol, 1997. 382(4): p. 459-68. 38. Stuelsatz, P., et al., A contemporary atlas of the mouse diaphragm: myogenicity, vascularity, and the Pax3 connection. J Histochem Cytochem, 2012. 60(9): p. 638-57. 39. Ackerman, K.G. and J.J. Greer, Development of the diaphragm and genetic mouse models of diaphragmatic defects. Am J Med Genet C Semin Med Genet, 2007. 145C(2): p. 109-16. 40. Holder, A.M., et al., Genetic factors in congenital diaphragmatic hernia. Am J Hum Genet, 2007. 80(5): p. 825-45. 41. Babiuk, R.P., et al., Embryological origins and development of the rat diaphragm. J Comp Neurol, 2003. 455(4): p. 477-87. 42. Dunwoodie, S.L., T.A. Rodriguez, and R.S. Beddington, Msg1 and Mrg1, founding members of a gene family, show distinct patterns of gene expression during mouse embryogenesis. Mech Dev, 1998. 72(1-2): p. 27-40. 43. Iritani, I., Experimental study on embryogenesis of congenital diaphragmatic hernia. Anat Embryol (Berl), 1984. 169(2): p. 133-9. 44. Allan, D.W. and J.J. Greer, Pathogenesis of nitrofen-induced congenital diaphragmatic hernia in fetal rats. J Appl Physiol (1985), 1997. 83(2): p. 338-47. 45. Mey, J., et al., Retinal dehydrogenase-2 is inhibited by compounds that induce congenital diaphragmatic hernias in rodents. Am J Pathol, 2003. 162(2): p. 673-9. 46. Clugston, R.D., et al., Teratogen-induced, dietary and genetic models of congenital diaphragmatic hernia share a common mechanism of pathogenesis. Am J Pathol, 2006. 169(5): p. 1541-9. 47. Merrell, A.J., et al., Muscle connective tissue controls development of the diaphragm and is a source of congenital diaphragmatic hernias. Nat Genet, 2015. 47(5): p. 496-504. 48. Buckingham, M., Skeletal muscle progenitor cells and the role of Pax genes. C R Biol, 2007. 330(6-7): p. 530-3. 49. Bladt, F., et al., Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature, 1995. 376(6543): p. 768-71. 50. Tajbakhsh, S., et al., Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD. Cell, 1997. 89(1): p. 127-38. 51. Tremblay, P., et al., A crucial role for Pax3 in the development of the hypaxial musculature and the long-range migration of muscle precursors. Dev Biol, 1998. 203(1): p. 49-61. 52. Dietrich, S., et al., The role of SF/HGF and c-Met in the development of skeletal muscle. Development, 1999. 126(8): p. 1621-9. 53. Yamamoto, Y., et al., Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons. Development, 1997. 124(15): p. 2903-13. 54. Clugston, R.D., W. Zhang, and J.J. Greer, Gene expression in the developing diaphragm: significance for congenital diaphragmatic hernia. Am J Physiol Lung Cell Mol Physiol, 2008. 294(4): p. L665-75. 55. Harrison, M.R., et al., A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA, 1994. 271(5): p. 382-4. 56. Ackerman, K.G. and B.R. Pober, Congenital diaphragmatic hernia and pulmonary hypoplasia: New insights from developmental biology and genetics. American Journal of Medical Genetics Part C-Seminars in Medical Genetics, 2007. 145c(2): p. 105-108. 57. Keller, R.L., Antenatal and postnatal lung and vascular anatomic and functional studies in congenital diaphragmatic hernia: implications for clinical management. Am J Med Genet C Semin Med Genet, 2007. 145C(2): p. 184-200. 58. Pober, B.R., Overview of epidemiology, genetics, birth defects, and chromosome abnormalities associated with CDH. American Journal of Medical Genetics Part C-Seminars in Medical Genetics, 2007. 145c(2): p. 158-171. 59. 陳加祥. 衛生福利部國民健康署遺傳疾病諮詢服務窗口. 2008; Available from: http://gene.hpa.gov.tw/index.php?mo=DiseasePaper&action=paper1_show&cate=Set2&csn=90&sn=424. 60. Russell, M.K., et al., Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes. Proc Natl Acad Sci U S A, 2012. 109(8): p. 2978-83. 61. Torfs, C.P., et al., A population-based study of congenital diaphragmatic hernia. Teratology, 1992. 46(6): p. 555-65. 62. Donnai, D. and M. Barrow, Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder? Am J Med Genet, 1993. 47(5): p. 679-82. 63. Slavotinek, A.M., Fryns syndrome: a review of the phenotype and diagnostic guidelines. Am J Med Genet A, 2004. 124A(4): p. 427-33. 64. Lin, I.C., et al., Recurrent congenital diaphragmatic hernia in Ehlers-Danlos syndrome. Cardiovasc Intervent Radiol, 2006. 29(5): p. 920-3. 65. Antonius, T., et al., Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation. Am J Med Genet A, 2008. 146A(4): p. 496-9. 66. Tautz, J., et al., Congenital diaphragmatic hernia and a complex heart defect in association with Wolf-Hirschhorn syndrome. Am J Med Genet A, 2010. 152A(11): p. 2891-4. 67. Schrier, S.A., et al., Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Am J Med Genet A, 2011. 155A(12): p. 3007-24. 68. Smigiel, R., et al., Co-occurrence of severe Goltz-Gorlin syndrome and pentalogy of Cantrell - Case report and review of the literature. Am J Med Genet A, 2011. 155A(5): p. 1102-5. 69. Christensen, P., Eventration of the diaphragm. Thorax, 1959. 14: p. 311-9. 70. Wayne, E.R., et al., Eventration of the diaphragm. J Pediatr Surg, 1974. 9(5): p. 643-51. 71. Smith, C.D., et al., Diaphragmatic paralysis and eventration in infants. J Thorac Cardiovasc Surg, 1986. 91(4): p. 490-7. 72. Obara, H., et al., Eventration of the diaphragm in infants and children. Acta Paediatr Scand, 1987. 76(4): p. 654-8. 73. Wu, S., et al., Congenital diaphragmatic eventration in children: 12 years' experience with 177 cases in a single institution. J Pediatr Surg, 2015. 50(7): p. 1088-92. 74. Shah-Mirany, J., G.L. Schmitz, and R.R. Watson, Eventration of the diaphragm. Physiologic and surgical significance. Arch Surg, 1968. 96(5): p. 844-50. 75. Bisgard, J.D., Congenital eventration of the diaphragm. J Thorac Surg, 1947. 16(5): p. 484-91. 76. Deslauriers, J., Eventration of the diaphragm. Chest Surg Clin N Am, 1998. 8(2): p. 315-30. 77. Tseng, B.S., et al., Pulmonary hypoplasia in the myogenin null mouse embryo. American Journal of Respiratory Cell and Molecular Biology, 2000. 22(3): p. 304-315. 78. Inanlou, M.R., et al., A significant reduction of the diaphragm in mdx : MyoD-/-(9th) embryos suggests a role for MyoD in the diaphragm development. Developmental Biology, 2003. 261(2): p. 324-336. 79. Babiuk, R.P. and J.J. Greer, Diaphragm defects occur in a CDH hernia model independently of myogenesis and lung formation. Am J Physiol Lung Cell Mol Physiol, 2002. 283(6): p. L1310-4. 80. Kluth, D., et al., Nitrofen-Induced Diaphragmatic-Hernias in Rats - an Animal-Model. Journal of Pediatric Surgery, 1990. 25(8): p. 850-854. 81. Clugston, R.D., et al., Understanding Abnormal Retinoid Signaling as a Causative Mechanism in Congenital Diaphragmatic Hernia. American Journal of Respiratory Cell and Molecular Biology, 2010. 42(3): p. 276-285. 82. Chitayat, D., et al., The PDAC syndrome (pulmonary hypoplasia/agenesis, diaphragmatic hernia/eventration, anophthalmia/microphthalmia, and cardiac defect) (Spear syndrome, Matthew-Wood syndrome): report of eight cases including a living child and further evidence for autosomal recessive inheritance. Am J Med Genet A, 2007. 143A(12): p. 1268-81. 83. Chassaing, N., et al., Phenotypic spectrum of STRA6 mutations: from Matthew-Wood syndrome to non-lethal anophthalmia. Hum Mutat, 2009. 30(5): p. E673-81. 84. Mendelsohn, C., et al., Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development, 1994. 120(10): p. 2749-71. 85. Goumy, C., et al., Retinoid pathway and congenital diaphragmatic hernia: hypothesis from the analysis of chromosomal abnormalities. Fetal Diagn Ther, 2010. 28(3): p. 129-39. 86. Brady, P.D., et al., Recent developments in the genetic factors underlying congenital diaphragmatic hernia. Fetal Diagn Ther, 2011. 29(1): p. 25-39. 87. Jay, P.Y., et al., Impaired mesenchymal cell function in Gata4 mutant mice leads to diaphragmatic hernias and primary lung defects. Dev Biol, 2007. 301(2): p. 602-14. 88. Garg, V., et al., GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature, 2003. 424(6947): p. 443-7. 89. Ackerman, K.G., et al., Fog2 is required for normal diaphragm and lung development in mice and humans. Plos Genetics, 2005. 1(1): p. 58-65. 90. Klaassens, M., et al., Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization. Am J Hum Genet, 2005. 76(5): p. 877-82. 91. You, L.R., et al., Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci U S A, 2005. 102(45): p. 16351-6. 92. Haruyama, N., A. Cho, and A.B. Kulkarni, Overview: engineering transgenic constructs and mice. Curr Protoc Cell Biol, 2009. Chapter 19: p. Unit 19 10. 93. Block, G.D., et al., Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium. Journal of Cell Biology, 1996. 132(6): p. 1133-1149. 94. Birchmeier, C., et al., Met, metastasis, motility and more. Nature Reviews Molecular Cell Biology, 2003. 4(12): p. 915-925. 95. Uehara, Y., et al., Rescue of embryonic lethality in hepatocyte growth factor/scatter factor knockout mice. Genesis, 2000. 27(3): p. 99-103. 96. Zorn, A.M., Liver development, in StemBook. 2008: Cambridge (MA). 97. Douarin, N.M., An experimental analysis of liver development. Med Biol, 1975. 53(6): p. 427-55. 98. Houssaint, E., Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. Cell Differ, 1980. 9(5): p. 269-79. 99. Medlock, E.S. and J.L. Haar, The liver hemopoietic environment: I. Developing hepatocytes and their role in fetal hemopoiesis. Anat Rec, 1983. 207(1): p. 31-41. 100. Wang, Z., et al., Retinoic acid regulates morphogenesis and patterning of posterior foregut derivatives. Dev Biol, 2006. 297(2): p. 433-45. 101. Berg, T., et al., Fibroblast growth factor 10 is critical for liver growth during embryogenesis and controls hepatoblast survival via beta-catenin activation. Hepatology, 2007. 46(4): p. 1187-97. 102. McLin, V.A., S.A. Rankin, and A.M. Zorn, Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development. Development, 2007. 134(12): p. 2207-17. 103. Yanai, M., et al., FGF signaling segregates biliary cell-lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro. Dev Dyn, 2008. 237(5): p. 1268-83. 104. Zhang, B., et al., Heparan sulfate deficiency disrupts developmental angiogenesis and causes congenital diaphragmatic hernia. J Clin Invest, 2014. 124(1): p. 209-21. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50063 | - |
| dc.description.abstract | Hepsin 為第二型穿膜絲胺酸蛋白酶，主要表現於肝臟。體外實驗已證實Hepsin 可活化人類第七凝血因子及肝細胞生長因子前驅物等，推測 Hepsin 可能參與血液凝固及肝細胞生長，但 Hepsin 基因剔除 (KO) 小鼠在血液凝固功能、肝臟重量及肝臟再生能力並無任何異常，故 Hepsin 實際生理功能目前仍不清楚。先前本實驗室研究發現 Hepsin 基因剔除小鼠橫膈膜面積、直徑及肝臟末緣至肋骨最後一節距離，皆顯著小於野生型 (WT) 小鼠。橫膈膜病理切片也發現中央肌腱 (central tendon) 區域較野生型小鼠薄。此外， Hepsin 基因剔除小鼠肺功能在乙醯甲膽鹼 (Methacholine) 刺激下其氣道阻力 (resistance) 與肺順應性 (compliance) 皆劣於野生型小鼠，推論 Hepsin 缺失可能造成小鼠橫膈膜發育異常，造成類似橫膈上提 (diaphragmatic eventration) 的病理現像。本篇論文利用表現人類 Hepsin 基因轉殖小鼠 (Tg-hHPN) 動物模式探討 Hepsin 是否參與橫膈膜發育及相關機制。實驗首先建立 Hepsin 基因轉殖小鼠，分別表達野生型 Hepsin (WT) 和蛋白酶無法活化之突變型 Hepsin (RS) ，取得親代小鼠 (Founder G0) 後再與 Hepsin 基因剔除鼠進行配種，並利用西方點墨法分析子代肝臟 Hepsin 表現量，挑選表現最高並建立穩定表現之基因轉殖小鼠。其中於Tg-hHPNWT品系建立 line-68與 line-5小鼠而在Tg-hHPNRS建立 line-39 與 line-54 小鼠。本論文以 G2 代基因小鼠為分析對象。結果顯示，表現人類 hepsin 的基因剔除小鼠 (Tg+-hHPN；HPN-/-) 其橫膈膜直徑、面積與肝臟末緣至肋骨最後一節距離，皆顯著大於 Hepsin 基因剔除小鼠。顯示重新表現人類 Hepsin 能援救橫膈膜於基因剔除小鼠的發育缺陷。為瞭解 Hepsin 蛋白在橫膈膜發育中所扮演的角色，本論文亦分析胚胎 (E13.5) 橫膈膜前驅結構pleuroperitoneal fold (PPF) 面積、肌肉前驅細胞 (muscle progenitors) 與纖維母細胞 (Fibroblast) 數量，結果顯示 hepsin 基因剔除鼠中 PPF 面積與纖維母細胞數目皆無差異，而肌肉前驅細胞數量較野生型少(但無顯著差異，待累積n值)。綜合上述結果， Hepsin 可能透過影響肌肉前驅細胞，進而影響橫膈膜中央肌腱的發育，造成類似橫膈上提的病理現象。 | zh_TW |
| dc.description.abstract | Hepsin, a type II transmembrane serine protease, is mainly expressed in the liver. It was investigated that in vitro Hepsin can activate the human factor VIIa and hepatocyte growth factor precursor (pro-HGF). It been proposed that Hepsin may be involved in blood coagulation and hepatocyte growth. Whereas Hepsin knockout mice have normal blood clotting function, liver weight and liver regeneration ability. The physiological function of hepsin remains unclear. In our previous studies showed that Hepsin knockout mice diaphragm area, diameter and the distance between liver edge to the last ribs are significantly less than the wild-type (WT) mice. Moreover, Diaphragm central tendon part of knockout mice was thinner than those in the wild-type mice. Under Methacholine stimulation, the airway resistance and lung compliance of Hepsin knockout mice was inferior to wild-type mice. It was proposed that the deficiency of Hepsin may induce the eventration of the diaphragm. In this studies, the human Hepsin transgene mice (Tg-hHPN) were used to investigate whether Hepsin participate in diaphragm development. Firstly, Tg-hHPN mice were established to express wild-type human Hepsin or the mutant form human Hepsin, HepsinRS. After obtaining the founders (G0), those mice crossed with Hepsin knockout mice. To obtain the highest and stable human Hepsin expressing transgene mice, the Hepsin expression level was detected in the liver of each founder offspring by Western blots. Wherein establishing the Tg-hHPNWT mice of line-68 and the line-5, strain and established the Tg-hHPNRS mice of line-39 and line-54.The G2 generation of the transgenic mice was used for the analisus in this study. The results showed that the diaphragm area, diameter and the distance between liver edge to the last ribs human Hepsin expressing with mice Hepsin-deficiency transgenic mice (Tg-hHPN; HPN - / -) of the significantly greater than Hepsin knockout mice. It showed that expression of human Hepsin can rescue developmental defects in the diaphragm in knockout mice. To understand the role of Hepsin in diaphragm development, we also measured diaphragm precursor structure the pleuroperitoneal folds (PPF) area and the number of muscle progenitors cell and Fibroblast in the transgene mive embryo (E13.5). The results showed that Hepsin knockout mouse had no difference in the PPF area and the number of fibroblasts, while the number of muscle precursor cells less than the wild-type (but no significant difference) continue to accrue n value). Based on the results, Hepsin may affect the muscle precursor cells, which resulted in the development of the central tendon in the diaphragm and caused diaphragm eventration. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:28:53Z (GMT). No. of bitstreams: 1 ntu-105-R03424015-1.pdf: 9799510 bytes, checksum: a8c193532393f4178266c8e3710a970f (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員審定書 ii
致謝 iii 中文摘要 iii 英文摘要 vi 圖目錄 x 表目錄 xi 第一章、緒論 - 1 - 前言 - 1 - Hepsin的組織分佈與蛋白結構 - 1 - Hepsin 功能探討 - 2 - Hepsin的病理角色 - 3 - 橫膈膜的功能與結構 - 4 - 橫膈膜的發育 - 5 - 橫膈膜疝氣 (diaphragmatic hernia) - 6 - 橫膈上提 (diaphragmatic eventration) - 7 - 橫膈膜缺陷相關機制 - 8 - 研究目的 - 10 - 第二章、材料與方法 - 11 - 實驗動物 - 11 - 人類 Hepsin基因轉殖小鼠之基因型鑑定 - 11 - 實驗動物犧牲與石蠟切片製作 - 11 - 小鼠橫膈膜解剖及型態觀察 - 12 - 免疫組織染色 - 12 - 組織染色 - 13 - 免疫組織螢光染色 - 14 - 小鼠肝臟蛋白萃取 - 14 - 西方墨點法 - 15 - 基因轉殖片段製備 - 16 - 顯微注射 - 16 - Pleuroperitoneal fold面積計算 - 16 - pleuroperitoneal fold中肌肉前驅細胞與纖維母細胞計算 - 16 - 數據分析與統計 - 17 - 第三章、實驗結果 - 18 - 利用基因轉殖技術建立表現人類 Hepsin 動物模式 - 18 - Tg-hHPNWT品系基因轉殖小鼠之建立 - 18 - Tg-hHPNRS品系編號39與54之建立 - 19 - Tg-hHPNWT基因轉殖小鼠肝臟末緣至肋骨最後一節距離與 Hepsin+/+ 小鼠無異 - 19 - Tg-hHPNWT基因轉殖公鼠的橫膈膜面積、橫膈膜橫向與縱向距離與 Hepsin-/- 小鼠無異 - 20 - Tg-hHPNWT與Tg-hHPNRS基因轉殖鼠肺臟重量與Hepsin+/+小鼠無異 - 22 - Hepsin-/- 小鼠 (E13.5) 胚胎 PPF 面積與 Hepsin+/+ 小鼠無異 - 23 - Hepsin-/- (E13.5) 胚胎 PPF 中肌肉前驅細胞較少 - 23 - 第四章、討論 - 25 - 以基因轉殖技術建立表現人類Hepsin小鼠動物模式 - 25 - 橫膈膜發育 - 26 - 肝臟組織異常生長未影響肺臟重量 - 27 - Hepsin缺乏疑似影響肌肉前驅細胞數量 - 28 - 未來實驗規劃 - 29 - 參考文獻 - 30 - 圖 - 37 - 表 - 68 - 附錄 - 70 - | |
| dc.language.iso | zh-TW | |
| dc.subject | 基因轉殖小鼠 | zh_TW |
| dc.subject | 基因轉殖小鼠 | zh_TW |
| dc.subject | Hepsin基因剔除小鼠 | zh_TW |
| dc.subject | 橫膈膜發育 | zh_TW |
| dc.subject | 先天性橫膈膜疝氣 | zh_TW |
| dc.subject | 橫膈上提 | zh_TW |
| dc.subject | pleuroperitoneal fold | zh_TW |
| dc.subject | pleuroperitoneal fold | zh_TW |
| dc.subject | 橫膈上提 | zh_TW |
| dc.subject | Hepsin基因剔除小鼠 | zh_TW |
| dc.subject | 先天性橫膈膜疝氣 | zh_TW |
| dc.subject | 橫膈膜發育 | zh_TW |
| dc.subject | pleuroperitoneal folds | en |
| dc.subject | Hepsin knockout mice | en |
| dc.subject | transgenic mice | en |
| dc.subject | diaphragm development | en |
| dc.subject | congenital diaphragmatic hernia | en |
| dc.subject | diaphragmatic eventration | en |
| dc.subject | pleuroperitoneal folds | en |
| dc.subject | Hepsin knockout mice | en |
| dc.subject | transgenic mice | en |
| dc.subject | diaphragm development | en |
| dc.subject | congenital diaphragmatic hernia | en |
| dc.subject | diaphragmatic eventration | en |
| dc.title | Hepsin 在橫膈膜發育的角色 | zh_TW |
| dc.title | The role of Hepsin in diaphragm development | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊雅倩(Ya-Chien Yang),林淑容(Shu-Rong Lin),黃祥博(Hsiang-Po Huang) | |
| dc.subject.keyword | Hepsin基因剔除小鼠,基因轉殖小鼠,橫膈膜發育,先天性橫膈膜疝氣,橫膈上提,pleuroperitoneal fold, | zh_TW |
| dc.subject.keyword | Hepsin knockout mice,transgenic mice,diaphragm development,congenital diaphragmatic hernia,diaphragmatic eventration,pleuroperitoneal folds, | en |
| dc.relation.page | 74 | |
| dc.identifier.doi | 10.6342/NTU201602085 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-08 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf 未授權公開取用 | 9.57 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。