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Cell Type Specific and Inducible Transgenesis in the Anterior Pituitary Gland

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Transgenic Models in Endocrinology

Abstract

With the recent emergence of the sequence for the human genome, and the inevitable wealth of DNA sequences that will be gathered from it, the use of genetic manipulation as a tool in uncovering the molecular basis of many physiological processes within the AP gland will become more apparent. The use of knockout and transgenic technologies has already been extremely useful in elucidating roles for many gene products. It is now well established that these approaches have their drawbacks, i.e. although the introduction or deletion of a particular gene may be useful for uncovering a particular rolein vivothe compensatory changes that are likely to occur during development may alter the animals phenotype. This would in turn affect the physiological process, which might occur in wild type animals. Viral vectors offer the possibility of creating transgenics in specific organs, tissues or even regions within a larger organ (i.e. brain nuclei) during adulthood. This offers a very powerful tool to not only express genes of interest, but also to ablate specific cell populations by expressing toxins or depleting specific mRNAs by expressing ribozymes. The possibilities of this technology are enormous both to uncover physiological effects, also for the development of experimental therapeutic strategies, for the treatment of human disease. In this chapter we will explore the possibility of expressing transgenes within specific cell populations in the anterior pituitary gland and the switching “on” and “off” of these exogenous genes.

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References

  1. de Keyzer Y, Rene P, Beldjord C, Leine F, Bertagna X. Overexpression of vasopressin (V3) and corticotrophin-releasing hormone receptor genes in corticotroph tumours. Clin Endocrinol 1998;49:475–82.

    Article  Google Scholar 

  2. Kottler ML, Seret-Begue D, Lahlou N, Assayag M, Carre MC, Lagarde JP, Ajzenberg C, Christin-Maitre S, Bouchard P, Mikol J, Couvis R, Warnet A. The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site. Clin Endocrinol 1998;49:115–23.

    Article  CAS  Google Scholar 

  3. Friend KE, Chiou YK, Lopes MB, Laws ER Jr., Hughes KM, Shupnik MA. Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas. J Clin Endocrinol Metab 1994;78:1497–504.

    Article  PubMed  CAS  Google Scholar 

  4. de Keyzer Y, Leine F, Bertagna X. Widespread transcription of the growth hormone-releasing peptide receptor gene in neuroendocrine human tumors. Eur J Endocrinol 1997;137:715–8.

    Article  PubMed  Google Scholar 

  5. Castro MG, Goya RG, Sosa YE, Rowe J, Larregina A, Morelli A, Lowenstein PR. Expression of transgenes in normal and neoplastic anterior pituitary cells using recombinant adenoviruses: long term expression, cell cycle dependency, and effects on hormone secretion. Endocrinology 1997;138:2184–94.

    Article  PubMed  CAS  Google Scholar 

  6. Neill JD, Musgrove LC, Duck LW, Sellers JC. High efficiency method for gene transfer in normal pituitary gonadotropes: adenoviral-mediated expression of G protein-coupled receptor kinase 2 suppresses luteinizing hormone secretion. Endocrinology 1999;140:2562–9.

    Article  PubMed  CAS  Google Scholar 

  7. Windeatt S, Southgate TD, Dewey RA, Bolognani F, Perone MJ, Larregina AT, Maleniak TC, Moms ID, Goya RG, Klatzmann D, Lowenstein PR, Castro MG. Adenovirusmediated herpes simplex virus type-1 thymidine kinase gene therapy suppresses oestrogen-induced pituitary prolactinomas. J Clin Endocrinol Metab 2000;85:1296–305.

    Article  PubMed  CAS  Google Scholar 

  8. Southgate TD, Windeatt S, Smith-Arica J, Gerdes CA, Perone MJ, Morris I, Davis JR, Klatzmann D, Lowenstein PR, Castro MG. Transcriptional targeting to anterior pituitary lactotrophic cells using recombinant adenovirus vectors in vitro and in vivo in normal and estrogen/sulpiride induced hyperplastic anterior pituitaries. Endocrinology 2000;141:3493–505.

    Article  PubMed  CAS  Google Scholar 

  9. Lee EJ, Thimmapaya B, Jameson JL. Stereotactic injection of adenoviral vectors that target gene expression to specific pituitary cell types: implications for gene therapy. Neurosurgery 2000;46:1461–9.

    Article  PubMed  CAS  Google Scholar 

  10. Forss-Petter S, Danielson PE, Catsicas S, Battenberg E, Price J, Nerenberg M, Sutcliffe JG. Transgenic mice expressing beta-galactosidase in mature neurons under neuron-specific enolase promoter control. Neuron 1990;5:187–97.

    Article  PubMed  CAS  Google Scholar 

  11. Morelli AE, Larregina AT, Smith-Arica J, Dewey RA, Southgate TD, Ambar B, Fontana A, Castro MG, Lowenstein PR. Neuronal and glial cell type-specific promoters within adenovirus recombinants restrict the expression of the apoptosis-inducing molecule Fas ligand to predetermined brain cell types, and abolish peripheral liver toxicity. J Gen Virol 1999;80:571–83.

    PubMed  CAS  Google Scholar 

  12. Navarro V, Millecamps S, Geoffroy MC, Robert JJ, Valin A, Mallet J, Gal La Salle G. Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter. Gene Ther 1999;6:1884–92.

    Article  PubMed  CAS  Google Scholar 

  13. Peel AL, Zolotukhin S, Schriomsher GW, Muzyczka N, Reier PJ. Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters. Gene Ther 1997;4:16–24.

    Article  PubMed  CAS  Google Scholar 

  14. Andersen JK, Frim DM, Isacson O, Breakfield XO. Herpesvirus-mediated gene delivery into the rat brain: specificity and efficiency of the neuron-specific enolase promoter. Cell Mol Neurobiol 1993;13:503–15.

    Article  PubMed  CAS  Google Scholar 

  15. Roemer K, Johnson PA, Friedmann T. Transduction of foreign regulatory sequences by a replication-defective herpes simplex virus type 1: the rat neuron-specific enolase promoter. Virus Res 1995;35:81–9.

    Article  PubMed  CAS  Google Scholar 

  16. Brenner M, Kisseberth WC, Su Y, Besnard F, Messing A. GFAP promoter directs astrocyte-specific expression in transgenic mice. J Neurosci 1994;14:1030–7.

    Google Scholar 

  17. Miyao Y, Shimizu K, Moriuchi S, Yamada M, Nakahira K, Nakajima K, Nakao J, Kuriyama S, Tsujii T, Mikoshiba K, Hayakawa T, Ikenaka K. Selective expression of foreign genes in glioma cells: Use of mouse myelin basic protein gene promoter to direct toxic gene expression. J Neurosci Res 1993;36:472–9.

    Article  PubMed  CAS  Google Scholar 

  18. Griscelli F, Gilardi-Hebenstreit P, Hanania N, Franz WM, Opolon P, Perricaudet M, Ragot T. Heart-specific targeting of beta-galactosidase by the ventricle-specific cardiac myosin light chain 2 promoter using adenovirus vectors. Hum Gene Ther 1998;9:1919–28.

    Article  PubMed  CAS  Google Scholar 

  19. Oh YJ, Moffat M, Wong S, Ullrey D, Geller AI, O’Malley KL. A herpes simplex virus-1 vector containing the rat tyrosine hydroxylase promoter directs cell type-specific expression of beta-galactosidase in cultured rat peripheral neurons. Brain Res Mol Brain Res 1996;35:227–36.

    Article  PubMed  CAS  Google Scholar 

  20. Miyatake SI, Tani S, Feigenbaum F, Sundaresan P, Toda H, Narumi O, Kikuchi H, Hashimoto N, Hangai M, Martuza RL, Rabkin, SD. Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo. Gene Ther 1999;6:564–72.

    Article  PubMed  CAS  Google Scholar 

  21. Hatzoglou M, Lamers W, Bosch F, Wynshaw-Boris A, Clapp DW, Hanson RW. Hepatic gene transfer in animals using retroviruses containing the promoter from the gene for phosphoenolpyruvate carboxykinase. J Biol Chem 1990;265:17285–93.

    PubMed  CAS  Google Scholar 

  22. Hatzoglou M, Park E, Wynshaw-Boris A, Kaung HL, Hanson RW. Hormonal regulation of chimeric genes containing the phosphoenol pyruvate carboxykinase promoter regulatory region in hepatoma cells infected by murine retroviruses. J Biol Chem 1988;263:1779–8808.

    Google Scholar 

  23. Hafenrichter DG, Ponder KP, Rettinger SD, Kennedy SC, Wu X, Saylors RS, Flye MW. Liver-directed gene therapy: evaluation of liver specific promoter elements. J Surg Res 1994;56:510–7.

    Article  PubMed  CAS  Google Scholar 

  24. Uto H, Ido A, Hori T, Hirono S, Hayashi K, Tamaoki T, Tsubouchi H. Hepatoma-specific gene therapy through retrovirus-mediated and targeted gene transfer using an adenovirus carrying the ecotropic receptor gene. Biochem Biophys Res Commun 1999;265:550–5.

    Article  PubMed  CAS  Google Scholar 

  25. Jager U, Zhao Y, Porter CD. Endothelial cell-specific transcriptional targeting from a hybrid long terminal repeat retrovirus vector containing human prepro-endothelin-1 promoter sequences. J Virol 1999;73:9702–9.

    PubMed  CAS  Google Scholar 

  26. Modlich U, Pugh CW, Bicknell R. Increasing endothelial cell specific expression by the use of heterologous hypoxic and cytokine-inducible enhancers. Gene Ther 2000;7:896–902.

    Google Scholar 

  27. Karpati G. Possible in vivo gene therapy of skeletal muscle in Duchenne muscular dystrophy. Gene Ther 1995;2:583–4.

    Google Scholar 

  28. Ferrari G, Salvatori G, Rossi C, Cossu G, Mavilio F. A retroviral vector containing a muscle-specific enhancer drives gene expression only in differentiated muscle fibers. Hum Gene Ther 1995;6:733–42.

    Article  PubMed  CAS  Google Scholar 

  29. Millecamps S, Kiefer H, Navarro V, Geoffroy MC, Robert JJ, Finiels F, Mallet J, Barkats M. Neuron-restrictive silencer elements mediate neuron specificity of adenoviral gene expression. Nat Biotech 1999;17:865–9.

    Article  CAS  Google Scholar 

  30. Chen H, McCarty DM, Bruce AT, Suzuki K. Oligodendrocyte-specific gene expression in mouse brain: use of a myelin-forming cell type-specific promoter in an adeno-associated virus. J Neurosci Res 1999;55:504–13.

    Article  PubMed  CAS  Google Scholar 

  31. Wang S, Bui V, Hughes JA, King MA, Meyer EM. Adeno-associated virus mediated gene transfer into primary rat brain neuronal and glial cultures: enhancement with the pH-sensitive surfactant dodecyl 2-(11-imidazolyl) propionate. Neurochem Int 2000;37:1–6.

    Article  PubMed  CAS  Google Scholar 

  32. Paterna JC, Moccetti T, Mura A, Feldon J, Bueler H. Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain. Gene Ther 2000;7:1304–11.

    Article  PubMed  CAS  Google Scholar 

  33. Wang L, Takabe K, Bidlingmaier SM, Ill CR, Verma 1M. Sustained correction of bleeding disorder in hemophilia B mice by gene therapy. Proc Natl Acad Sci USA 1999;96:3906–10.

    Article  PubMed  CAS  Google Scholar 

  34. Kurpad C, Mukherjee P, Wang XS, Ponnazhagan S, Li L, Yoder MC, Srivastava A. Adeno-associated virus 2-mediated transduction and erythroid lineage-restricted expression from parvovirus B 19p6 promoter in primary human hematopoietic progenitor cells. J Hematother Stem Cell Res 1999;8:585–92.

    Article  PubMed  CAS  Google Scholar 

  35. Albarracin CT, Frosch MP, Chin WW. The gonadotropin-releasing hormone receptor gene promoter directs pituitary-specific oncogene expression in transgenic mice. Endocrinology 1999;140:2415–21.

    Article  PubMed  CAS  Google Scholar 

  36. Rene P, Leine F, Ventura M, Bertagna X, de Keyzer Y. Nucleotide sequence and structural organization of the human vasopressin pituitary receptor (V3) gene. Gene 2000;241:57–64.

    Article  PubMed  CAS  Google Scholar 

  37. Jaffrain-Rea ML, Petrangeli E, Lubrano C, Minniti G, Di Stefano D, Sciarra F, Frati L, Tamburrano G, Cantore G, Gulino A. Epidermal growth factor binding sites in human pituitary macroadenomas. J Endocrinology 1998;158:425–33.

    Article  CAS  Google Scholar 

  38. Daniel L, Trouillas J, Renaud W, Chevallier P, Gouvernet J, Rougon G, Figarella-Branger D. Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. Cancer Res 2000;60:80–5.

    PubMed  CAS  Google Scholar 

  39. Lee EJ, Anderson LM, Thimmapaya B, Jameson, JL. Targeted expression of toxic genes directed by pituitary hormone promoters: a potential strategy for adenovirus-mediated gene therapy of anterior pituitary tumors. J Clin Endocrinol Metab 1999;84:786–94.

    Article  PubMed  CAS  Google Scholar 

  40. Castro MG, Windeatt S, Smith-Arica J, Lowenstein PR. Cell-type specific expression in the pituitary: physiology and gene therapy. Biochem Soc Trans 1999;27:858–63.

    PubMed  CAS  Google Scholar 

  41. Kraus J, Buchfelder M, Hollt V. Regulatory elements of the human proopiomelanocortin gene promoter. DNA Cell Biol 1993;12:527–36.

    Article  PubMed  CAS  Google Scholar 

  42. Pierce JG, Parsons TF. Glycoprotein hormones: structure and function. Annu Rev Biochem 1981;50:465–95.

    Article  PubMed  CAS  Google Scholar 

  43. Haugen BR, McDermott MT, Gordon DF, Rupp CL, Wood WM, Ridgeway EC. Determinants of thyrotrope-specific thyrotropin beta promoter activation: Cooperation of Pit-1 with another factor. J Biol Chem 1996;271:385–9.

    Article  PubMed  CAS  Google Scholar 

  44. Wurm FM, Gwinn KA, Kingston RE. Inducible overproduction of the mouse c-myc protein in mammalian cells. Proc Natl Acad Sci USA, 1986;83:5414–8.

    Article  PubMed  CAS  Google Scholar 

  45. Mayo KE, Warren R, Palmiter RD. The mouse metallothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. Cell 1982;29:99–108.

    Article  PubMed  CAS  Google Scholar 

  46. Ryals J, Dierks P, Ragg H, Weissmann C. A 46-nucleotide promoter segment from an IFN-alpha gene renders an unrelated promoter inducible by virus. Cell 1985;41:497–507.

    Article  PubMed  CAS  Google Scholar 

  47. Lee F, Mulligan R, Berg P, Ringold G. Glucocorticoids regulate expression of dihydrofolate reductase cDNA in mouse mammary tumour virus chimaeric plasmids. Nature 1981;294:228–32.

    Article  PubMed  CAS  Google Scholar 

  48. Hynes NE, Groner B. Mammary tumor formation and hormonal control of mouse mammary tumor virus expression. Curr Top Microbiol Immunol 1982;101:51–74.

    Article  PubMed  CAS  Google Scholar 

  49. Palmiter RD, Chen HY, Brinster RL. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell, 1982;29:701–10.

    Article  PubMed  CAS  Google Scholar 

  50. Wang Y, O’Malley BW Jr, Tsai SY, Olvlalley BW. A regulatory system for use in gene transfer. Proc Nat Acad Sci USA 1994;91:8180–4.

    Article  PubMed  CAS  Google Scholar 

  51. Molin M, Shoshan MC, Ohman-Forslund K, Linder S, Akusjarvi G. Two novel adenovirus vector systems permitting regulated protein expression in gene transfer experiments. J Virol 1998;72:8358–61.

    PubMed  CAS  Google Scholar 

  52. Abruzzese RV, Godin D, Burcin M, Mehta V, French M, Li Y, O’Malley BW, Nordstrom JL. Ligand-dependent regulation of plasmid-based transgene expression in vivo. Hum Gene Ther 1999;10:1499–1507.

    Article  PubMed  CAS  Google Scholar 

  53. Burcin MM, Schiedner G, Kochanek S, Tsai SY, O’Malley BW. Adenovirus-mediated regulable target gene expression in vivo. Proc Natl Acad Sci USA 1999;96 355–60.

    Article  PubMed  CAS  Google Scholar 

  54. Wan Y, DeMayo FJ, Tsai SY, O’Malley BW. Ligand-inducible and liver specific target gene expression in transgenic mice. Nat Biotechnol 1997;15:239–43.

    Article  Google Scholar 

  55. Serguera C, Bohl D, Rolland E, Prevost R, Herard TM. Control of erythropoietin secretion by doxycycline or mifepristone in mice bearing polymer-encapsulated engineered cells. Hum Gene Ther 1999;10:375–83.

    Article  PubMed  CAS  Google Scholar 

  56. No D, Yao TP, Evans RM. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 1996;93:3346–51.

    Article  PubMed  CAS  Google Scholar 

  57. Rivera VM, Clackson T, Natesan S, Pollock R, Amara JF, Keenan T, Magari SR, Phillips T, Courage NL, Cerasoli F Jr, Holt DA, Gilman M. A humanized system for pharmacologic control of gene expression. Nat Med 1996;2:1028–32.

    Article  PubMed  CAS  Google Scholar 

  58. Rivera VM, Ye X, Courage NL, Sachar J, Cerasoli F Jr, Wilson JM, Gilman M. Longterm regulated expression of growth hormone in mice after intramuscular gene transfer. Proc Natl Acad Sci USA 1999;96:8657–62.

    Article  PubMed  CAS  Google Scholar 

  59. Dunlop J, Lou Z, Mcllvain HB. Steroid Hormone-Inducible Expression of the GLT-1 Subtype of High-Affinity 1-Glutamate Transporter in Human Embryonic Kidney Cells. Biochem Biophys Res Commun 1999;265:101–5.

    Article  PubMed  CAS  Google Scholar 

  60. Johns DC, Marx R, Mains RE, ORourke B, Marban E. Inducible genetic suppression of neuronal excitability. J Neurosci 1999;19:1691–7.

    PubMed  CAS  Google Scholar 

  61. Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Nail Acad Sci USA 1992;89:5547–51.

    Article  CAS  Google Scholar 

  62. Agha-Mohammadi S, Lotze MT. Regulatable systems: applications in gene therapy and replicating viruses. J Clin Invest 2000;105:1177–83.

    Article  PubMed  CAS  Google Scholar 

  63. Beck CF, Mutzel R, Barbé J, Muller W. A multifunctional gene (tetR) controls Tn10encoded tetracycline resistance. J Bacteriol 1982;150:633–42.

    PubMed  CAS  Google Scholar 

  64. Takahashi M, Altsclunied L, Hillen W. Kinetic and equilibrium characterisation of the Tet repressor-tetracycline complex by fluorescence measurements. Evidence for divalent metal ion requirement and energy transfer. J Mol Biol 1986;187:341–8.

    Article  PubMed  CAS  Google Scholar 

  65. Hinrichs W, Kisker C, Duvel M, Muller A, Tovar K, Hillen W, Saenger W. Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance. Science 1994;264:418–420.

    Article  PubMed  CAS  Google Scholar 

  66. Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science 1995;268:1766–9.

    Article  PubMed  CAS  Google Scholar 

  67. Baron U, Schnappinger D, Helbl V, Gossen M, Hillen W, Bujard H. Generation of conditional mutants in higher eukaryotes by switching between the expression of two genes. Proc Nati Acad Sci USA 1999;96:1013–8.

    Article  CAS  Google Scholar 

  68. Urlinger S, Baron U, Thelhnann M, Hasan MT, Bujard H, Hillen W. Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. Proc Natl Acad Sci USA 2000;97:7963–8.

    Article  PubMed  CAS  Google Scholar 

  69. Yoshida Y, Hamada H. Adenovirus-mediated inducible gene expression through tetracycline-controllable transactivator with nuclear localization signal. Biochem Biophys Res Commun 1997;230:426–30.

    Article  PubMed  CAS  Google Scholar 

  70. Gossen M, Bujard H. Efficacy of tetracycline-controlled gene expression is influenced by cell type: commentary. Biotechniques 1995;19:213–6.

    PubMed  CAS  Google Scholar 

  71. Harding TC, Geddes JB, Noel JD, Murphy D, Uney JB. Tetracycline-regulated transgene expression in hippocampal neurones following transfection with adenoviral vectors. J Neurochem 1997;69:2620–3.

    Article  PubMed  CAS  Google Scholar 

  72. Harding TC, Geddes BJ, Murphy D, Knight D, Uney JB. Switching transgene expression in the brain using an adenoviral tetracycline-regulatable system. Nat Biotech 1998;16:553–5.

    Article  CAS  Google Scholar 

  73. Corti O, Horellou P, Colin P, Cattaneo E, Mallet J. Intracerebral tetracycline-dependent regulation of gene expression in grafts of neural precursors. NeuroReport 1996;7:1655–9.

    Article  PubMed  CAS  Google Scholar 

  74. Corti O, Sabate O, Horellou P, Colin P, Dumas S, Buchet D, Buc-Caron MH, Mallet J. A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors. Nat Biotech 1999;17:349–54.

    Article  CAS  Google Scholar 

  75. Hu SX, Ji W, Zhou Y, Logothetis C, Xu HJ. Development of an adenoviral vector with tetracycline-regulatable human tumour necrosis factor alpha gene expression. Cancer Res 1997;57:3339–43.

    PubMed  CAS  Google Scholar 

  76. Massie B, Couture F, Lamoureux L, Mosser DD, Guilbault C, Jolicoeur P, Belanger F, Langelier Y. Inducible overexpression of a toxic protein by an adenovirus vector with a tetracycline-regulatable expression cassette. J Virol 1998;72:2289–96.

    PubMed  CAS  Google Scholar 

  77. Rubinchik S, Ding R, Qiu AJ, Zhang F, Dong J. Adenoviral vector which delivers FasLGFP fusion protein regulated by the tet-inducible expression system. Gene Ther 2000;7:875–85.

    Article  PubMed  CAS  Google Scholar 

  78. Hofmann A, Nolan GP, Blau HM. Rapid retroviral delivery of tetracycline-inducible genes in a single autoregulatory cassette. Proc Natl Acad Sci USA 1996;93:5185–90.

    Article  PubMed  CAS  Google Scholar 

  79. Paulus W, Baur I, Boyce FM, Breakefield XO, Reeves SA. Self-contained, tetracycline-regulated retroviral vector system for gene delivery to mammalian cells. J Virol 1996;70:62–7.

    PubMed  CAS  Google Scholar 

  80. Ho DY, McLaughlin JR, Sapoisky RM. Inducible gene expression from defective herpes simplex virus vectors using the tetracycline-responsive promoter system. Brain Res Mol Brain Res 1996;41:200–9.

    Article  PubMed  CAS  Google Scholar 

  81. Rendahl KG, Leff SE, Otten GR, Spratt SK, Bohl D, Van Roey M, Donahue BA, Cohen LK, Mandel RJ, Danos O, Snyder RO. Regulation of gene expression in vivo following transduction by two separate rAAV vectors. Nat Biotech 1998;16:757–61.

    Article  CAS  Google Scholar 

  82. Kim HJ, Gatz C, Hillen W, Jones TR. Tetracycline repressor-regulated gene repression in recombinant human cytomegalovirus. J Virol 1995;69:2565–73.

    PubMed  CAS  Google Scholar 

  83. Paulus W, Baur I, Oberer DM, Breakefield XO, Reeves SA. Regulated expression of the diphtheria toxin A gene in human glioma cells using prokaryotic transcriptional control elements. J Neurosurg 1997;87:89–95.

    Article  PubMed  CAS  Google Scholar 

  84. Agha-Mohammadi S, Alvarez-Vallina L, Ashworth LJ, Hawkins RE. Delay in resumption of the activity of tetracycline-regulatable promoter following removal of tetracycline analogues. Gene Ther 1997;4:993–7.

    Article  Google Scholar 

  85. Lowenstein PR, Southgate TD, Smith-Arica JR, Smith J, Castro MG. Gene therapy for inherited neurological disorders: towards therapeutic intervention in the Lesch-Nyhan syndrome. Prog Brain Res 1998;117:485–501.

    Article  PubMed  CAS  Google Scholar 

  86. Huang CJ, Spinella F, Nazarian R, Lee MM, Dopp JM, de Vellis J. Expression of green fluorescent protein in oligodendrocytes in a time and level-controllable fashion with a tetracycline-regulated system. Mol Med 1999;5:129–37.

    PubMed  CAS  Google Scholar 

  87. Efrat S, Fusco-DeMane D, Lemberg H, al Emran O, Wang X. Conditional transformation of a pancreatic beta-cell line derived from transgenic mice expressing a tetracycline-regulated oncogene. Proc Natl Acad Sci USA 1995;92:3576–80.

    Article  PubMed  CAS  Google Scholar 

  88. Yu JS, Sena-Esteves M, Paulus W, Breakefield XO, Reeves SA. Retroviral delivery and tetracycline-dependent expression of IL-1beta converting enzyme (ICE) in a rat glioma model provides controlled induction of apoptotic death in tumor cells. Cancer Res 1996;56:5423–7.

    PubMed  CAS  Google Scholar 

  89. Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lubbert H, Bujard H. Doxycyline-mediated quantitative and tissue-specific control of genome expression in transgenic mice. Proc Natl Acad Sci USA 1996;93:10933–8.

    Article  PubMed  CAS  Google Scholar 

  90. Mansuy IM, Winder DG, Moallem TM, Osman M, Mayford M, Hawkins RD, Kandel ER. Inducible and reversible gene expression with the rtTA system for the study of memory. Neuron 1998;21:257–65.

    Article  PubMed  CAS  Google Scholar 

  91. Mansuy IM, Mayford M, Jacob B, Kandel ER, Bach ME. Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 1998;92:39–49.

    Article  PubMed  CAS  Google Scholar 

  92. Chen J, Bezdek T, Chang J, Kherzai AW, Willingham T, Azzara M, Nisen PD. A glial-specific, repressible, adenovirus vector for brain tumor gene therapy. Cancer Res 1998;58:3504–7.

    PubMed  CAS  Google Scholar 

  93. Smith-Arica JR, Morelli AE, Larregina AT, Smith J, Lowenstein PR, Castro MG. Cell-type specific and regulatable transgenesis in the adult brain: adenovirus-encoded combined transcriptional targeting and inducible transgene expression. Mol Ther 2000;2:579–587

    Article  PubMed  CAS  Google Scholar 

  94. Ralph GS, Bienemann A, Harding TC, Hopton M, Henley J, Uney, JB. Targeting of tetracycline-regulatable transgene expression specifically to neuronal and glial cell populations using adenoviral vectors. Neuroreport 2000;11:2051–5.

    Article  PubMed  CAS  Google Scholar 

  95. Utomo AR, Nikitin AY, Lee, WH. Temporal, spatial and cell type-specific control of Cremediated DNA recombination in transgenic mice. Nat Biotech 1999;17:1091–6.

    Article  CAS  Google Scholar 

  96. Smith-Arica JR, Williams JC, Stone D, Smith J, Lowenstein PR, Castro MG. Switching on and off transgene expression within lactotrophic cells in the anterior pituitary gland in vivo. Endocrinology 2000 (Submitted).

    Google Scholar 

  97. Ghersa P, Gobert RP, Sattonnet-Roche P, Richards CA, Merlo Pich E, Hooft van Huijsduijnen R. Highly controlled gene expression using combinations of a tissue-specific promoter, recombinant adenovirus and a tetracycline-regulatable transcription factor. Gene Ther 1998;5:1213–20.

    Article  PubMed  CAS  Google Scholar 

  98. Southgate TD, Stone D, Williams JC, Lowenstein PR, Castro MG. Long term transgene expression within the anterior pituitary gland in situ: impact on circulating hormone levels, cellular and antibody mediated immune reponses. Endocrinology 2001;142:464–476

    Article  PubMed  CAS  Google Scholar 

  99. Kajiwara K, Byrnes AP, Ohmoto Y, Charlton HM, Wood MJ, Wood KJ. Humoral immune responses to adenovirus vectors in the brain. J Neuroimmunol 2000;103:8–15.

    Article  PubMed  CAS  Google Scholar 

  100. Yang Y, Nimes FA, Berencsi K, Furth EE, Gonczol E, Wilson JM. Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 1994;91:4407–11.

    Article  PubMed  CAS  Google Scholar 

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Castro, M.G. et al. (2001). Cell Type Specific and Inducible Transgenesis in the Anterior Pituitary Gland. In: Castro, M.G. (eds) Transgenic Models in Endocrinology. Endocrine Updates, vol 13. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1633-0_11

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  • DOI: https://doi.org/10.1007/978-1-4615-1633-0_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5651-6

  • Online ISBN: 978-1-4615-1633-0

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