PTA1/CD226转基因小鼠胸腺细胞的发育研究
摘要
目的：建立四环素调控的mPTA1／CD226转基因小鼠，对转基因小鼠胸腺细胞的发育进行研究。
方法：①使用pcDNA3-mPTA1和pBI-5载体构建用于四环素调控转基因小鼠制备的pBI-5-mPTA1载体。②采用显微注射的方法将pBI-5-mPTA1载体片段导入B6D1F1小鼠受精卵，对新生小鼠耳成纤维细胞进行体外培养，用含rtTA的pUHD17.1质粒转染细胞，选出荧光素酶表达活性依赖Dox的小鼠。③将阳性小鼠与正常C57BL／6小鼠交配，分别使用mPTA1和荧光素酶(luciferase)引物对子代小鼠的基因组DNA进行PCR检测和鉴定，选取双阳性的Ptet-mPTA1转基因小鼠的F1代，将其继续与C57BL／6小鼠交配，不断得到子代小鼠，直至F4代以后。④将阳性的Ptet-mPTA1转基因小鼠与携带有tTA的EμSR-tTA转基因小鼠杂交，得到子代小鼠，同时使用mPTA1和tTA引物对其基因组DNA进行PCR检测，选取mPTA1和tTA双阳性的小鼠。⑤使用荧光素酶检测试剂盒对杂交的阳性小鼠的不同组织，如胸腺、脾脏、心脏、肾脏等进行
Objective: To establish the conditional tetracycline-regulated transgenic mice overexpressing mouse platelet and T cell activation antigen 1 (mPTA1) , and study the development of thymocytes in the transgenic mice.
Method: The mPTAl expression vector was constructed by recombination of pcDNA3-mPTA1 and pBI-5, and the transgenic mouse lines were generated by microinjection using standard techniques. Positive animals were selected based on analysis of DNA sequence from mouse tails by PCR. The controlled regulation of the integrated expression unit was tested by transfection of the primary mouse ear fibroblasts obtained from DNA positive founders with the rtTA plasmid pUHD-17.1. Founder animals that showed DOX dependent expression of luciferase were selected and interbred with C57BL/6 mice to establish F1 of P_(tet)mPTA1 transgenic mice with defined genetic background.
Double-transgenic animals containing the luciferase/mPTA1 transcription and expression tTA in thymocytes were obtained by crossing individuals of
方法：①使用pcDNA3-mPTA1和pBI-5载体构建用于四环素调控转基因小鼠制备的pBI-5-mPTA1载体。②采用显微注射的方法将pBI-5-mPTA1载体片段导入B6D1F1小鼠受精卵，对新生小鼠耳成纤维细胞进行体外培养，用含rtTA的pUHD17.1质粒转染细胞，选出荧光素酶表达活性依赖Dox的小鼠。③将阳性小鼠与正常C57BL／6小鼠交配，分别使用mPTA1和荧光素酶(luciferase)引物对子代小鼠的基因组DNA进行PCR检测和鉴定，选取双阳性的Ptet-mPTA1转基因小鼠的F1代，将其继续与C57BL／6小鼠交配，不断得到子代小鼠，直至F4代以后。④将阳性的Ptet-mPTA1转基因小鼠与携带有tTA的EμSR-tTA转基因小鼠杂交，得到子代小鼠，同时使用mPTA1和tTA引物对其基因组DNA进行PCR检测，选取mPTA1和tTA双阳性的小鼠。⑤使用荧光素酶检测试剂盒对杂交的阳性小鼠的不同组织，如胸腺、脾脏、心脏、肾脏等进行
Objective: To establish the conditional tetracycline-regulated transgenic mice overexpressing mouse platelet and T cell activation antigen 1 (mPTA1) , and study the development of thymocytes in the transgenic mice.
Method: The mPTAl expression vector was constructed by recombination of pcDNA3-mPTA1 and pBI-5, and the transgenic mouse lines were generated by microinjection using standard techniques. Positive animals were selected based on analysis of DNA sequence from mouse tails by PCR. The controlled regulation of the integrated expression unit was tested by transfection of the primary mouse ear fibroblasts obtained from DNA positive founders with the rtTA plasmid pUHD-17.1. Founder animals that showed DOX dependent expression of luciferase were selected and interbred with C57BL/6 mice to establish F1 of P_(tet)mPTA1 transgenic mice with defined genetic background.
Double-transgenic animals containing the luciferase/mPTA1 transcription and expression tTA in thymocytes were obtained by crossing individuals of
引文
1 Shortman K and Wu L. Early T lymphocyte progenitor. Annu Rev Immunol. 1996, 14: 29-47
2 Juan Carlos Zuniga-Pflucker. T-cell development made simple. Nat Rev Immunol. 2004, 4: 67-72
3 Jason Gill, et al. Thymic generation and regeneration. Immunol Rev. 2003, 195: 28-50
4 Godfrey DI, et al. A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8-triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol. 1993, 150: 4244-52
5 Ceredig, R and Rolink T. A positive look at double-negative thymocytes. Nature Rev Immunol. 2002, 2: 888-897
6 Wolfer A, Wilson A, Nemir M, et al. Inactivation of Notchl impairs VDJ rearrangement and allows pre-TCR-independent survival of early lineage thymocytes. Immunity. 2002, 16: 869-879
7 Harald yon Boehmer and Hans Jorg Fehling. Structure and function of the pre-T cell receptor. Annu Rev Immunol. 1997, 15: 433-452
8 Timothy K Starr, Stephen C Jameson, and Kristin A Hogquist. Positive and negative selection ofT cells. Annu Rev Immunol. 2003, 21: 139-76
9 Philippe Bousso, Nirav R Bhakata, Richard S Lewis, and Ellen Robey. Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy. Science. 2002, 296: 1876-188010 Eric Hailman, W Richard Burack, Andrey S Shaw, Michael L Dustin, and Paul M Allen. Immature CD4+CD8+ thymocytes form a multifocal immunological synapse with sustained tyrosine phosphorylation. Immunity. 2002,16: 839-848
11 Sung-Joo E Lee, Yuko Hori, and Arup K Chakraborty. Low T cell receptor expression and thermal fluctuation contribute to formation of dynamic multifocal synapses in thymocytes. PNAS. 2003, 100: 4383-4388
12 Lisa M Minter and Barbara A Osborne. Cell death in the thymus - it's all a matter of contacts. Seminars in Immunology. 2003, 15: 135-144
13 Pellicci DG, Hammond KJL, Uldrich AP, Baxter A, Smyth MJ, Godfrey DI. NKT cells develop through a thymus-dependent NK1.1-CD4+ CD1d-dependent precursor stage. J Exp Med. 2002,195:835-844
14 Gordon F Burns, Tony Triglia, Jerome A Werkmeister, et al. TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. J. Exp. Med. 1985,161:1063-1078
15 Judith L Scott, Stephanie M Dunn, Boquan Jin, et al. Characterization of a novel membrane glycoprotein involved in platelet activation. J. Bio. Chem. 1989,264: 13475-13482
16 Jia W, Liu XS, Zhu Y, et al. Preparation and characterization of mAbs against different epitopes of CD226 (PTA1). Hybridoma. 2000,19(6):489-494
17 Akira Shibuya, David Campbell, Charles Hannum, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996,4: 573-58118 Cristina Bottino, Roberta Castriconi, Daniela Pende, Paola Rivera, Marina Nanni, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003, 198: 557-567
19 Akira Shibuya, Lewis L Lanier, Joseph H Phillips. Protein kinase C is involved in the regulation of both signalling and adhesion medicated by DNAX accessory molecule-1 receptor. J. Immunol. 1998, 161: 1671-1676
20 Kazuko Shibuya, Jun Shirakawa, Tomie Kameyama, et al. CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med. 2003, 198: 1829-1839
21 Kylie J Ralston, Samantha L Hird, Xinhai Zhang, Judith L. Scott, Boquan Jin, et al. The LFA-1-associated molecule PTA1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large. J Biol Chem. 2004, 279: 33816-33828
22 Lihua Chen, Xin Xie, Xinhai Zhang, et al. The expression, regulation and adhesion function of a novel CD molecule, CD226, on human endothelial cells. Life Sciences. 2003, 73: 2373-2382
23 张赟，贾卫，韩卫宁等．CD226分子在NK细胞亚群上的表达规律与能关系的研究．中国免疫学杂志，2004，20(8)：14-17
24 Zuzel M, Waiton S, Bums GF, et al. A monoclonal antibody to a 67kD cell membrane glycoprotein directly induces persistent platelet aggregation independently of granule secretion. Brit J Haematol. 1991, 79: 466-47325 孙忱，金伯泉，孙凯．PTA1单克隆抗体诱导人血小板活化聚集和胞浆Ca~(2+)水平的升高．中华血液学杂志．1998，19(3)：133-135
26 Mendelsohn CL, Wimmer E, Racaniello VR. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell. 1989, 56(5): 855-865
27 Eberle F, Dubreuil P, Mattei MG, et al. The human PRR2 gene, related to the human poliovirus receptor gene(PVR), is the true homolog of the murine MPH gene. Gene. 1995, 159(2): 267-272
28 Lopez M, Aoubala M, Jordier F, et al. The human poliovirus receptor related 2 protein is a new hemotopoietic/endothelial homophilic adhesion molecule. Blood. 1998, 92(12): 4602-4611
29 Pende D, Bottino C, Castriconi R, et al. PVR(CD155) and Nectin-2(CD112) as ligands of the human DNAM-1(CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol. 2005, 42(4): 463-469
30 Tomasec P, Wang EC, Davision AJ, et al. Downregulation of natural killer cell-activating ligand CD 155 by human cytomegalovirus UL141. Nat Immunol. 2005, 6(2): 181-188
31 张新海，李德敏，欧阳为明，贾卫，谢鑫，陈丽华，宁双飞，张赞，金伯泉．小鼠CD226(PTA1)的基因克隆及其异型．中国免疫学杂志．2002，18(6)：371-375
32 徐向升，张赞，张新海等．小鼠PTA1／CD226分子参与杀伤性T细胞(CTL)的分化．中华微生物学和免疫学杂志．2006，26(1)：32-35
33 张新海．小鼠PTA1／CD226分子的基因克隆及其表达、分布和功能研究(博士论文)，第四军医大学，2003年5月：103-104
34 M. E. Morrison, V. R. Racaniello. Molecular cloning and expression of a murine homolog of the human poliovirus receptor gene. J. Virol. 1992, 66:??2807-2813.
35 Satako TH, Akitomo M, Ayumi Hara, et al. Identification and characterization of murine DNAM-1 (CD226) and its poliovirus receptor family ligands. Biochem Biophys Res Commun. 2005, 329(3):996-1000.
36 Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH. Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci USA. 1980, 77:7380 - 7384
37 Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA. 1992,89:5547-5551
38 Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science. 1995,268:1766-1769
39 Zhou Zhu, Tao Zheng, Chun G Lee, et al. Tetracycline-controlled transcriptional regulation systems: advances and application in transgenic animal modeling. Semin Cell Dev Biol. 2002 ,13(2):121-128
40 Elke Ueberham, Rainer Low, Uwe Ueberham, et al. Conditional tetracycline-regulated expression of TGF-beta1 in liver of transgenic mice leads to reversible intermediary fibrosis. Hepatology. 2003, 37(5): 1067-78
41 Dragan Marinkovic, Tatjana Marinkovic, Bettina Mahr, Jochen Hess, and Thomas Wirth. Reversible lymphomagenesis in conditionally c-MYC expressing mice. Int J Cancer. 2004, 110(3):336-342.
42 Dean W.Felsher and J.Michael Bishop. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell. 1999,4(2): 199-207
43 Priscilla A.Furth, Luc St Onge, Hinrich Boger, et al. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci U S A. 1994, 1(20):9302-6
44 Kazunori Yukawa, Hitoshi Kikutani, Takeaki Inomoto, et al. Strain??dependency of B and T lymphoma development in immunoglobulin heavy chain enhancer (Eμ)-myc transgenic mice. J Exp Med. 1989, 170(3):711-26
45 Yutaka Takebe, Motoharu Seiki, Jun-ichi Fujisawa, et al. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988, 8(1):466-72.
46 Andreas Kistner, Manfred Gossen, Frank Zimmermann, et al. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci U S A. 1996, 93(20): 10933-8.
47 Dardalhon V, Schubart AS, Reddy J, et al. CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. J Immunol. 2005, 175(3):1558-65.
48 Revilla C, et al. Treatment with anti-LFA-1α monoclonal antibody selectively interferes with the maturation of CD4-CD8+ thymocytes. Immunology. 1997,90: 550-556
49 Tao Deng, Shangwu Liu, Qun Wu, Yan Liu, Wei Ju, Junyan Liu, Feili Gong, Boquan Jin, and Jinquan Tan. CD226 expression deficiency causes high sensitivity to apoptosis in natural killer T cells from patients with systemic lupus erythematosus. J Immunol. 2005,174: 1281-1290
50 Xing Z, Conway EM, Kang C, Winoto A. Essential role of surviving, an inhibitor of apoptosis protein, in T cell development, maturation, and homeostasis. J Exp Med. 2004,199: 69-80
51 Kobayashi Y, Yukiue H, Sasaki H, Fukai I, Yokoyama T, Kiriyama M, Yamakawa Y, Maeda M, Fujii Y. Developmentally regulated expression of surviving in the human thymus. Hum Immunol 2002,63: 101-107
52 Okada H, Bakal C, Shahinian A, Elia A, Wakeham A, Suh WK, DuncanGS, Ciofani M, Rottapel R, Zuniga-Pflucker JC, Mak TW. Survivin loss in thymocytes triggers p53-mediated growth arrest and p53-independent cell death. J Exp Med 2004, 199: 399-410
2 Juan Carlos Zuniga-Pflucker. T-cell development made simple. Nat Rev Immunol. 2004, 4: 67-72
3 Jason Gill, et al. Thymic generation and regeneration. Immunol Rev. 2003, 195: 28-50
4 Godfrey DI, et al. A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8-triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol. 1993, 150: 4244-52
5 Ceredig, R and Rolink T. A positive look at double-negative thymocytes. Nature Rev Immunol. 2002, 2: 888-897
6 Wolfer A, Wilson A, Nemir M, et al. Inactivation of Notchl impairs VDJ rearrangement and allows pre-TCR-independent survival of early lineage thymocytes. Immunity. 2002, 16: 869-879
7 Harald yon Boehmer and Hans Jorg Fehling. Structure and function of the pre-T cell receptor. Annu Rev Immunol. 1997, 15: 433-452
8 Timothy K Starr, Stephen C Jameson, and Kristin A Hogquist. Positive and negative selection ofT cells. Annu Rev Immunol. 2003, 21: 139-76
9 Philippe Bousso, Nirav R Bhakata, Richard S Lewis, and Ellen Robey. Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy. Science. 2002, 296: 1876-188010 Eric Hailman, W Richard Burack, Andrey S Shaw, Michael L Dustin, and Paul M Allen. Immature CD4+CD8+ thymocytes form a multifocal immunological synapse with sustained tyrosine phosphorylation. Immunity. 2002,16: 839-848
11 Sung-Joo E Lee, Yuko Hori, and Arup K Chakraborty. Low T cell receptor expression and thermal fluctuation contribute to formation of dynamic multifocal synapses in thymocytes. PNAS. 2003, 100: 4383-4388
12 Lisa M Minter and Barbara A Osborne. Cell death in the thymus - it's all a matter of contacts. Seminars in Immunology. 2003, 15: 135-144
13 Pellicci DG, Hammond KJL, Uldrich AP, Baxter A, Smyth MJ, Godfrey DI. NKT cells develop through a thymus-dependent NK1.1-CD4+ CD1d-dependent precursor stage. J Exp Med. 2002,195:835-844
14 Gordon F Burns, Tony Triglia, Jerome A Werkmeister, et al. TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. J. Exp. Med. 1985,161:1063-1078
15 Judith L Scott, Stephanie M Dunn, Boquan Jin, et al. Characterization of a novel membrane glycoprotein involved in platelet activation. J. Bio. Chem. 1989,264: 13475-13482
16 Jia W, Liu XS, Zhu Y, et al. Preparation and characterization of mAbs against different epitopes of CD226 (PTA1). Hybridoma. 2000,19(6):489-494
17 Akira Shibuya, David Campbell, Charles Hannum, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996,4: 573-58118 Cristina Bottino, Roberta Castriconi, Daniela Pende, Paola Rivera, Marina Nanni, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003, 198: 557-567
19 Akira Shibuya, Lewis L Lanier, Joseph H Phillips. Protein kinase C is involved in the regulation of both signalling and adhesion medicated by DNAX accessory molecule-1 receptor. J. Immunol. 1998, 161: 1671-1676
20 Kazuko Shibuya, Jun Shirakawa, Tomie Kameyama, et al. CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med. 2003, 198: 1829-1839
21 Kylie J Ralston, Samantha L Hird, Xinhai Zhang, Judith L. Scott, Boquan Jin, et al. The LFA-1-associated molecule PTA1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large. J Biol Chem. 2004, 279: 33816-33828
22 Lihua Chen, Xin Xie, Xinhai Zhang, et al. The expression, regulation and adhesion function of a novel CD molecule, CD226, on human endothelial cells. Life Sciences. 2003, 73: 2373-2382
23 张赟，贾卫，韩卫宁等．CD226分子在NK细胞亚群上的表达规律与能关系的研究．中国免疫学杂志，2004，20(8)：14-17
24 Zuzel M, Waiton S, Bums GF, et al. A monoclonal antibody to a 67kD cell membrane glycoprotein directly induces persistent platelet aggregation independently of granule secretion. Brit J Haematol. 1991, 79: 466-47325 孙忱，金伯泉，孙凯．PTA1单克隆抗体诱导人血小板活化聚集和胞浆Ca~(2+)水平的升高．中华血液学杂志．1998，19(3)：133-135
26 Mendelsohn CL, Wimmer E, Racaniello VR. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell. 1989, 56(5): 855-865
27 Eberle F, Dubreuil P, Mattei MG, et al. The human PRR2 gene, related to the human poliovirus receptor gene(PVR), is the true homolog of the murine MPH gene. Gene. 1995, 159(2): 267-272
28 Lopez M, Aoubala M, Jordier F, et al. The human poliovirus receptor related 2 protein is a new hemotopoietic/endothelial homophilic adhesion molecule. Blood. 1998, 92(12): 4602-4611
29 Pende D, Bottino C, Castriconi R, et al. PVR(CD155) and Nectin-2(CD112) as ligands of the human DNAM-1(CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol. 2005, 42(4): 463-469
30 Tomasec P, Wang EC, Davision AJ, et al. Downregulation of natural killer cell-activating ligand CD 155 by human cytomegalovirus UL141. Nat Immunol. 2005, 6(2): 181-188
31 张新海，李德敏，欧阳为明，贾卫，谢鑫，陈丽华，宁双飞，张赞，金伯泉．小鼠CD226(PTA1)的基因克隆及其异型．中国免疫学杂志．2002，18(6)：371-375
32 徐向升，张赞，张新海等．小鼠PTA1／CD226分子参与杀伤性T细胞(CTL)的分化．中华微生物学和免疫学杂志．2006，26(1)：32-35
33 张新海．小鼠PTA1／CD226分子的基因克隆及其表达、分布和功能研究(博士论文)，第四军医大学，2003年5月：103-104
34 M. E. Morrison, V. R. Racaniello. Molecular cloning and expression of a murine homolog of the human poliovirus receptor gene. J. Virol. 1992, 66:??2807-2813.
35 Satako TH, Akitomo M, Ayumi Hara, et al. Identification and characterization of murine DNAM-1 (CD226) and its poliovirus receptor family ligands. Biochem Biophys Res Commun. 2005, 329(3):996-1000.
36 Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH. Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci USA. 1980, 77:7380 - 7384
37 Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA. 1992,89:5547-5551
38 Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science. 1995,268:1766-1769
39 Zhou Zhu, Tao Zheng, Chun G Lee, et al. Tetracycline-controlled transcriptional regulation systems: advances and application in transgenic animal modeling. Semin Cell Dev Biol. 2002 ,13(2):121-128
40 Elke Ueberham, Rainer Low, Uwe Ueberham, et al. Conditional tetracycline-regulated expression of TGF-beta1 in liver of transgenic mice leads to reversible intermediary fibrosis. Hepatology. 2003, 37(5): 1067-78
41 Dragan Marinkovic, Tatjana Marinkovic, Bettina Mahr, Jochen Hess, and Thomas Wirth. Reversible lymphomagenesis in conditionally c-MYC expressing mice. Int J Cancer. 2004, 110(3):336-342.
42 Dean W.Felsher and J.Michael Bishop. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell. 1999,4(2): 199-207
43 Priscilla A.Furth, Luc St Onge, Hinrich Boger, et al. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci U S A. 1994, 1(20):9302-6
44 Kazunori Yukawa, Hitoshi Kikutani, Takeaki Inomoto, et al. Strain??dependency of B and T lymphoma development in immunoglobulin heavy chain enhancer (Eμ)-myc transgenic mice. J Exp Med. 1989, 170(3):711-26
45 Yutaka Takebe, Motoharu Seiki, Jun-ichi Fujisawa, et al. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988, 8(1):466-72.
46 Andreas Kistner, Manfred Gossen, Frank Zimmermann, et al. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci U S A. 1996, 93(20): 10933-8.
47 Dardalhon V, Schubart AS, Reddy J, et al. CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. J Immunol. 2005, 175(3):1558-65.
48 Revilla C, et al. Treatment with anti-LFA-1α monoclonal antibody selectively interferes with the maturation of CD4-CD8+ thymocytes. Immunology. 1997,90: 550-556
49 Tao Deng, Shangwu Liu, Qun Wu, Yan Liu, Wei Ju, Junyan Liu, Feili Gong, Boquan Jin, and Jinquan Tan. CD226 expression deficiency causes high sensitivity to apoptosis in natural killer T cells from patients with systemic lupus erythematosus. J Immunol. 2005,174: 1281-1290
50 Xing Z, Conway EM, Kang C, Winoto A. Essential role of surviving, an inhibitor of apoptosis protein, in T cell development, maturation, and homeostasis. J Exp Med. 2004,199: 69-80
51 Kobayashi Y, Yukiue H, Sasaki H, Fukai I, Yokoyama T, Kiriyama M, Yamakawa Y, Maeda M, Fujii Y. Developmentally regulated expression of surviving in the human thymus. Hum Immunol 2002,63: 101-107
52 Okada H, Bakal C, Shahinian A, Elia A, Wakeham A, Suh WK, DuncanGS, Ciofani M, Rottapel R, Zuniga-Pflucker JC, Mak TW. Survivin loss in thymocytes triggers p53-mediated growth arrest and p53-independent cell death. J Exp Med 2004, 199: 399-410