Clinical and Experimental Nephrology

, Volume 1, Issue 3, pp 157–178 | Cite as

Strategic gene transfer into the kidney: Current status and prospects

  • Masanori Kitamura
Review Article


Progress in gene transfer technology has established the scientific basis for molecular approaches to human diseases. In the kidney, the first trial of gene transfer was reported in 1991, and several strategies have been developed during the past years. Successful gene transfer into specific renal structures allows for evaluation of in vivo effects of certain molecules on the structure and function of the kidney. It would also be useful for therapeutic intervention in renal diseases by introducing “beneficial” genes into the affected sites. By introducing viral vectors or liposomes via particular access routes, it is feasible to selectively manipulate function of certain renal structures. Through the renal circulation, exogenous genes can be targeted to the vasculature, glomeruli and proximal tubules. Using a retrograde approach via the urinary tract, access to collecting ducts is possible. Implantation of genetically modified cells under the capsule of the kidney allows for diffusion of transgene products into the interstitium. Transplantation of embryonic metanephric kidneys also provides a biological window for renal gene transfer. Furthermore, germline gene manipulations are becoming realistic strategies for creation of “transgenic kidneys” and “gene knockout kidneys.” This article summarizes the current experince with gene transfer into the kidney and addresses its potential impact on nephrology.

Key words

gene trasfer gene therapy adenovirus liposome oligonucleotide 


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  1. 1.
    Jackson DA, Symons RH, Berg P. Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon ofEscherichia coli. Proc. Natl Acad Sci USA 1972; 69:2904–2909.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Cohen SN, Chang AC, Boyer HW, Helling RB. Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA 1973;70:3240–3244.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Jaenisch R, Mintz B. Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Proc Natl Acad Sci USA 1974;71:1250–1254.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Ledley FD. Nonviral gene therapy: the promise of genes as pharmaceutical products. Human Gene Ther 1995; 6:1129–1144.CrossRefGoogle Scholar
  5. 5.
    Jolly D. Viral vector system for gene therapy. Cancer Gene Ther 1994;1:51–64.PubMedGoogle Scholar
  6. 6.
    Herskowitz I. Functional inactivation of genes by dominant negative mutations. Nature 1987; 329:219–222.PubMedCrossRefGoogle Scholar
  7. 7.
    Stein CA, Cheng Y-C, Antisense oligonucleotides as therapeutic agents—is the bullet really magical? Science 1993;261:1004–1012.PubMedCrossRefGoogle Scholar
  8. 8.
    Cech TR. Ribozymes and their medical implications. JAMA 1988;260:3030–3034.PubMedCrossRefGoogle Scholar
  9. 9.
    Capecchi MR. Altering the genome by homologous recombination Science 1989;244:1288–1292.PubMedCrossRefGoogle Scholar
  10. 10.
    Culver KW. Gene Therapy. A handbook for physicians. New York: Mary Ann Liebert Publisher, 1994.Google Scholar
  11. 11.
    Koseki C, Herzlinger D, Al-Awqati Q. Integration of embryonic nephrogenic cells carrying a reporter gene into functioning nephrons. Am J Physiol 1991;261:C550-C554.PubMedCrossRefGoogle Scholar
  12. 12.
    Kitamura M. Genetic manipulation of the kidney: round one. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:109–111.Google Scholar
  13. 13.
    Imai E, Isaka Y, Akagi Y, Kaneda Y. Gene transfer into the glomerulus by hemagglutinating virus of Japan (HVJ)-liposome method. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:112–117.Google Scholar
  14. 14.
    Lien YH, Lai LW. Liposome-mediated gene transfer into the tubules. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:132–136.Google Scholar
  15. 15.
    Sukhatme VP, Cowley BD, Zhu G. Gene transfer into kidney tubules and vasculature by adenoviral vectors. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:137–143.Google Scholar
  16. 16.
    Kitamura M. Gene delivery into the glomerulus via mesangial cell vectors. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:118–125.Google Scholar
  17. 17.
    Kelley VR, Moore KJ. Application of a gene transfer strategy to identify molecules that incite autoimmune kidney injury. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997; 5:144–151.Google Scholar
  18. 18.
    Woolf AS. Genetic manipulation of the embryonic kidney. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:152–156.Google Scholar
  19. 19.
    Kopp JB. Gene expression in kidney using transgenic approaches. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:157–167.Google Scholar
  20. 20.
    Matsusaka T, Ichikawa I. Gene targeting in nephrology. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:168–173.Google Scholar
  21. 21.
    Palmiter RD, Brinster RL. Germ-line transformation of mice. Annu Rev Genet 1986;20: 465–499.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Furth PA, Onge LS, Boger H, Gruss P, Gossen M, Kistner A, Bujard H, Hennighausen L. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci USA 1994;91:9302–9306.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Milligan JF, Matteucci MD, Martin JC. Current concepts in antisense drug design. J Med Chem 1993; 36:1923–1937.PubMedCrossRefGoogle Scholar
  24. 24.
    Wagner RW. Gene inhibition using antisense oligodeoxynucleotides. Nature 1994;372:333–335.PubMedCrossRefGoogle Scholar
  25. 25.
    Morishita R, Gibbons GH, Horiuchi M, Nakajima M, Zhang L, Kaneda Y, Ogihara T, Dzau VJ. A novel molecular strategy usingcis element decoy of E2F binding site inhibits smooth muscle proliferation in vivo. Proc Natl Acad Sci USA 1995;92:5855–5859.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Tomita N, Morishita R, Higaki J, Ogihara T. A novel strategy for gene therapy and gene regulation analysis using transcription factor decoy oligonucleotides. Exp Nephrol 1997 (in press).Google Scholar
  27. 27.
    Branch AD, Klotman PE. Optimizing ribozymes for somatic cell gene therapy. Exp Nephrol 1997 (in press).Google Scholar
  28. 28.
    Kitamura M, Ishikawa Y. Functional inactivation of signaling molecules via transdominant negative mutants. Exp Nephrol 1997 (in press).Google Scholar
  29. 29.
    Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL. Direct gene transfer into mouse muscle in vivo. Science, 1990;247:1465–1468.PubMedCrossRefGoogle Scholar
  30. 30.
    Larrick JW, Burck KL. Gene therapy: application of molecular biology. New York: Elsevier, 1991:71–104.Google Scholar
  31. 31.
    Larrick JW, Burck KL: Gene therapy: application of molecular biology. New York: Elsevier, 1991:105–160.Google Scholar
  32. 32.
    Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, Muller D, Lupien PJ, Wilson JM. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nature Genet 1994;6:335–341.PubMedCrossRefGoogle Scholar
  33. 33.
    Breakefield XO. Gene delivery into the brain using viral vectors. Nature Genet 1993;3:187–189.PubMedCrossRefGoogle Scholar
  34. 34.
    Nabel EG, Plautz G, Nabel GJ. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science 1990;249:1285–1288.PubMedCrossRefGoogle Scholar
  35. 35.
    Rosenfeld MA, Siegfried W, Yoshimura K, Yoneyama K, Fukayama M, Stier LE, Paakko PK, Gilardi P, Stratford-Perricaudet LD, Perricaudet M, Jallat S, Pavirani A, Lecocq J-P, Crystal RG. Adenovirus-mediated transfer of a recombinant α1-antitrypsin gene to the lung epithelium in vivo. Science 1991;252:431–434.PubMedCrossRefGoogle Scholar
  36. 36.
    Yang Y, Paper SE, Cohn JA, Engelhardt JF, Wilson JM. An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer. Proc Natl Acad Sci USA 1993;90:4601–4605.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Moullier P, Friedlander G, Calise D, Ronco P, Perricaudet M, Ferry N. Adenoviral-mediated gene transfer to renal tubular cells in vivo. Kidney Int 1994;45:1220–1225.PubMedCrossRefGoogle Scholar
  38. 38.
    Stratford-Perricaudet LD, Makeh I, Perricaudet M, Briand P. Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest 1992;90:626–630.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Zhu N, Liggitt D, Liu Y, Debs R. Systemic gene expression after intravenous DNA delivery into adult mice. Science 1993;261:209–211.PubMedCrossRefGoogle Scholar
  40. 40.
    Wolff JA. Gene therapeutics: methods and applications of direct gene transfer. Boston: Birkhauser, 1994.CrossRefGoogle Scholar
  41. 41.
    Tomita N, Higaki J, Morishita R, Kato K, Mikami H, Kaneda Y, Ogihara T. Direct in vivo gene introduction into rat kidney. Biochem Biophys Res Commun 1992; 186:129–134.PubMedCrossRefGoogle Scholar
  42. 42.
    Kaneda Y, Iwai K, Uchida T. Increased expression of DNA cointroduced with nuclear protein in adult rat liver. Science 1989;243:375–378.PubMedCrossRefGoogle Scholar
  43. 43.
    Isaka Y, Fujiwara Y, Ueda N, Kaneda Y, Kamada T, Imai E. Glomerulosclerosis induced by in vivo transfection of transforming growth factor-β or platelet derived growth factor gene into the rat kidney. J Clin Invest 1993;92:2597–2601.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Arai M, Wada A, Isaka Y, Akagi Y, Sugiura T, Miyazaki M, Moriyama T, Kaneda Y, Naruse K, Naruse M, Orita Y, Ando A, Kamada T, Ueda N, Imai E. In vivo transfection of genes for renin and angiotensinogen into the glomerular cells induced phenotypic change of the mesangial cells and glomerular sclerosis. Biochem Biophys Res Commun 1995;206:525–532.PubMedCrossRefGoogle Scholar
  45. 45.
    Yura T, Fukunaga M, Munger KA, Imai E, Badr KF. In vivo transfection of human arachidonate 15-lipoxygenase gene into the rat kidney: impact on nephrotoxic serum nephritis. J Am Soc Nephrol 1995;6:890 (abstr).Google Scholar
  46. 46.
    Akagi Y, Isaka Y, Arai M, Kaneko T, Takenaka M, Moriyama T, Kaneda Y, Ando A, Orita Y, Kamada T, Ueda N, Imai E. Inhibition of TGF-β1 expression by antisense oligonucleotides suppressed extracellular matrix accumulation in experimental glomerulonephritis. Kidney Int 1996;50:148–155.PubMedCrossRefGoogle Scholar
  47. 47.
    Kashihara N, Maeshima Y, Makino H. Therapeutic intervention in glomerulonephritis by oligonucleotides. In: Kitamura M (ed) Genetic manipulation of the kidney. Exp Nephrol 1997;5:126–131.Google Scholar
  48. 48.
    Chang H, Katoh T, Noda M, Kanegae Y, Saito I, Asano S, Kurokawa K. Highly efficient adenovirus-mediated gene transfer into renal cells in culture. Kidney Int 1995;47:322–326.PubMedCrossRefGoogle Scholar
  49. 49.
    Heikkila P, Parpala T, Lukkarinen O, Weber M, Tryggvason, K. Adenovirus-mediated gene transfer into kidney glomeruli using an ex vivo and in vivo kidney perfusion system—first step towards gene therapy of Alport syndrome. Gene Ther 1996;3:21–27.PubMedGoogle Scholar
  50. 50.
    Zhu G, Nicolson AG, Cowley BD, Rosen S, Sukhatme VP. In vivo adenovirus-mediated gene transfer into normal and cystic rat kidneys. Gene Ther 1996;3:298–304.PubMedGoogle Scholar
  51. 51.
    Strayer DS. SV40 as an effective gene transfer vector in vivo. J Biol Chem 1996;271:24741–24746.PubMedGoogle Scholar
  52. 52.
    Kitamura M, Taylor S, Unwin R, Burton S, Shimizu F, Fine LG. Gene transfer into the rat renal glomerulus via a mesangial cell vector: site-specific delivery, in situ amplification and sustained expression of an exogenous gene in vivo. J Clin Invest 1994;94:497–505.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Kitamura M, Burton S, Yokoo T, Fine LG. Gene delivery into the renal glomerulus by transfer of genetically engineered, autologous mesangial cells. Exp Nephrol 1996;4:56–59.PubMedGoogle Scholar
  54. 54.
    Kitamura M, Burton S, English J, Kawachi H, Fine LG. Transfer of a mutated gene encoding active transforming growth factor-β1 suppresses mitogenesis and IL-1 response in the glomerulus. Kidney Int 1995; 48:1747–1757.PubMedCrossRefGoogle Scholar
  55. 55.
    Yokoo T, Kitamura M. Gene transfer of interleukin-1 receptor antagonist into the renal glomerulus via a mesangial cell vector. Biochem Biophys Res Commun 1996;226:883–888.PubMedCrossRefGoogle Scholar
  56. 56.
    Kitamura M. Creation of a reversible on/off system for site-specific in vivo control of exogenous gene activity in the renal glomerulus. Proc Natl Acad Sci USA 1996;93:7387–7391.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Kitamura M, Kawachi H. Creation of an in vivo cytosensorusing genetically engineered mesangial cells: automatic sensing of glomerular inflammation controls transgene activity. J Clin Invest 1997;100:1394–1399.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Kitamura M, Sütö TS. Transfer of genetically engineered macrophages into the glomerulus. Kidney Int 1997;51:1274–1279.PubMedCrossRefGoogle Scholar
  60. 60.
    Sütö TS, Fine LG, Shimizu F, Kitamura M. In vivo transfer of engineered macrophages into the glomerulus: endogenous TGF-β-mediated defense against macrophage-induced glomerular cell activation. J Immunol 1997;159:2476–2483.PubMedGoogle Scholar
  61. 61.
    Rosen H, Gordon S. Adoptive transfer of fluorescencelabeled cells shows that resident peritoneal macrophages are able to migrate into specialized lymphoid organs and inflammatory sites in the mouse. Eur J Immunol 1990;20:1251–1258.PubMedCrossRefGoogle Scholar
  62. 62.
    Holdsworth SR, Neale TJ. Macrophage induced glomerular injury. Cell transfer studies in passive autologous antiglomerular basement membrane antibody-initiated experimental glomerulonephritis. Lab Invest 1984;51:172–180.PubMedGoogle Scholar
  63. 63.
    Lan HY, Nikolic-Paterson DJ, Atkins RC. Trafficking of inflammatory macrophages from the kidney to draining lymph nodes during experimental glomerulonephritis. Clin Exp Immunol 1993;92:336–341.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Woolf AS, Palmer SJ, Snow ML, Fine LG. Creation of a functioning chimeric mammalian kidney. Kidney Int 1990;38:991–997.PubMedCrossRefGoogle Scholar
  65. 65.
    Woolf AS, Bosch RJ, Fine LG. Gene transfer into the mammalian kidney: microtransplantation of retrovirus-transduced metanephric tissue. Exp Nephrol 1993;1:41–48.PubMedGoogle Scholar
  66. 66.
    Bosch RJ, Woolf AS, Fine LG. Gene transfer into the mammalian kidney: direct retrovirus transduction of regenerating tubular epithelial cells. Exp Nephrol 1993;1:49–54.PubMedGoogle Scholar
  67. 67.
    Lipkowitz MS, Hanss N, Tulchin N, Wilson PD, Kurtzman GJ, Klotman PE, Klotman ME. Transduction of renal cells in vitro and in vivo by adeno-associated virus gene therapy vectors. J Am Soc Nephrol 1996;7:1617 (abstr).Google Scholar
  68. 68.
    Sands H, Gorey-Feret LJ, Cocuzza AJ, Hobbs FW, Chidester D, Trainor GL. Biodistribution and metabolism of internally3H-labeled oligonucleotides. I. Comparison of a phosphodiester and a phosphorothioate. Mol Pharmacol 1994;45:932–943.PubMedGoogle Scholar
  69. 69.
    Rappaport J, Hanss B, Kopp JB, Copeland TD, Bruggeman LA, Coffman TM, Klotman PE. Transport of phosphorothioate oligonucleotides in kidney: implications for molecular therapy. Kidney Int 1995; 47:1462–1469.PubMedCrossRefGoogle Scholar
  70. 70.
    Oberbauer R, Schreiner GF, Biber J, Murer H, Meyer TW. In vivo suppression of the renal Na+/Pi cotransporter by antisense oligonucleotides. Proc Natl Acad Sci USA 1996;93:4903–4906.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Noiri E, Peresleni T, Miller F, Goligorsky MS. In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest 1996;97:2377–2383.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Haller H, Dragun D, Miethke A, Park JK, Weis A, Lippoldt A, Grob V, Luft FC. Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat. Kidney Int 1996;50:473–480.PubMedCrossRefGoogle Scholar
  73. 73.
    Zeigler ST, Kerby JD, Curiel DT, Diethelm AG, Thompson JA. Molecular conjugate-mediated gene transfer into isolated human kidneys. Transplantation 1996;61:812–817.PubMedCrossRefGoogle Scholar
  74. 74.
    Naito T, Yokoyama H, Moore KJ, Dranoff G, Mulligan RC, Kelley VR. Macrophage growth factors introduced into the kidney initiate renal injury. Mol Med 1996;2:297–312.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Naito T, Moore KJ, Kelley VR. IL-6 neither promotes nor suppresses renal injury. Am J Physiol 1996; 271:F603-F609.PubMedGoogle Scholar
  76. 76.
    Moore KJ, Yeh K, Naito T, Kelley VR. TNF-α enhances colony-stimulating factor-1-induced macrophage accumulation in autoimmune renal disease. J Immunol 1996;157:427–432.PubMedGoogle Scholar
  77. 77.
    Moore KJ, Naito T, Martin C, Kelley V-R. Enhanced response of macrophages to CSF-1 in autoimmune mice: a gene transfer strategy. J Immunol 1996;157:433–440.PubMedGoogle Scholar
  78. 78.
    Moore KJ, Barbee SD, Wada T, Kelley VR. Gene transfer of Rantes into the MRL-FAS kidney incites renal injury. J Am Soc Nephrol 1996;7:1710 (abstr).Google Scholar
  79. 79.
    Grobstein C. Morphogenetic interaction between embryonic mouse tissues separated by a membrane filter. Nature 1953;172:869–871.PubMedCrossRefGoogle Scholar
  80. 80.
    Sariola H. Does the kidney express redundant or important molecules during nephrogenesis? In: Woolf AS (ed) Nephrogenesis. Exp Nephrol 1996;4:70–76.Google Scholar
  81. 81.
    Saliola H, Saarma M, Sainio K, Arumae U, Palgi J, Vaahtokari A, Thesleff I, Karavanov A. Nerve growth factor receptor is required for kidney morphogenesis. Science 1991;254:571–573.CrossRefGoogle Scholar
  82. 82.
    Rothenpieler UW, Dressler GRPax-2 is required for mesenchyme-to-epithelium conversion during kidney development. Development 1993;119:711–720.PubMedGoogle Scholar
  83. 83.
    Wada J, Liu ZZ, Alvares K, Kumar A, Wallner E, Makino H, Kanwar YS. Cloning of cDNA for the alpha subunit of mouse insulin-like growth factor I receptor and the role of the receptor in metanephric development. Proc Natl Acad Sci USA 1993;90:10360–10364.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Liu ZZ, Kumar A, Wallner EI, Wada J, Carone FA, Kanwar YS. Trophic effect of insulin-like growth factor-I on metanephric development: relationship to proteoglycans. Eur J Cell Biol 1994;65:378–391.PubMedGoogle Scholar
  85. 85.
    Kanwar YS, Liu ZZ, Kumar A, Wada J, Carone FA. Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins. Kidney Int 1995;48:1646–1659.PubMedCrossRefGoogle Scholar
  86. 86.
    Vukicevic S, Kopp JB, Luyten FP, Sampath TK. Induction of nephrogenic mesenchyme by osteogenic protein 1 (bone morphogenetic protein 7). Proc Natl Acad Sci USA 1996;93:9021–9026.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Wada J, Kumar A, Liu Z, Ruoslahti E, Reichardt L, Marvaldi J, Kanwar YS. Cloning of mouse integrin alphaV cDNA and role of the alphaV-related matrix receptors in metanephric development. J. Cell Biol 1996;132:1161–1176.PubMedCrossRefGoogle Scholar
  88. 88.
    Herzlinger D, Qiao J, Cohen D, Ramakrishna N, Brown AM. Induction of kidney epithelial morphogenesis by cells expressingWnt-1. Dev Biol 1994;166:815–818.PubMedCrossRefGoogle Scholar
  89. 89.
    Herzlinger D, Koseki C, Mikawa T, Al-Awqati Q Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction. Development 1992;114:565–572.PubMedGoogle Scholar
  90. 90.
    Burrow CR, Wilson PD Renal progenitor cells: problems of definition, isolation, and characterization. Exp Nephrol 1994;2:1–12.PubMedGoogle Scholar
  91. 91.
    Woolf AS, Kolatsi-Joannou M, Hardman P, Andermarcher E, Moorby C, Fine LG, Jat PS, Noble MD, Gherardi E. Roles of hepatocyte growth factor/scatter factor andmet in early development of the metanephros. J Cell Biol 1995;128:171–184.PubMedCrossRefGoogle Scholar
  92. 92.
    Coutelle C, Douar, A-M, Colledge WH, Froster U. The challenge of fetal gene therapy. Nature Med 1995; 1:864–866.PubMedCrossRefGoogle Scholar
  93. 93.
    Tsukamoto M, Ochiya T, Yoshida S, Sugimura T, Terada M. Gene transfer and expression in progeny after intravenous DNA injection into pregnant mice. Nature Genet 1995;9:243–248.PubMedCrossRefGoogle Scholar
  94. 94.
    Kopp JB, Klotman PE. Transgenic animal models of renal development and pathogenesis. Am J Physiol 1995;269:F601–620.PubMedCrossRefGoogle Scholar
  95. 95.
    Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R. WT-1 is required for early kidney development. Cell 1993; 74:679–691.PubMedCrossRefGoogle Scholar
  96. 96.
    Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 1994;367:319–320.CrossRefGoogle Scholar
  97. 97.
    Stark K, Vainio S, Vassileva G, McMahon AP. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 1994;372:679–683.PubMedCrossRefGoogle Scholar
  98. 98.
    Shawlot W, Behringer RR. Requirement forLim1 in head-organizer function. Nature 1995;374:425–432.PubMedCrossRefGoogle Scholar
  99. 99.
    Dudley AT, Lyons KM, Robertson EJ. A requirement of bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 1995; 9:2795–2807.PubMedCrossRefGoogle Scholar
  100. 100.
    Luo G, Hofmann C, Bronckers ALJJ, Sohocki M, Bradley A, Karsenty G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 1995;9:2808–2820.PubMedCrossRefGoogle Scholar
  101. 101.
    Threadgill DW, Dlugosz AA Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC, Barnard JA, Yuspa SH, Coffey RJ, Magnuson T. Target disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 1995;269:230–234.PubMedCrossRefGoogle Scholar
  102. 102.
    Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 1996;382:70–73.PubMedCrossRefGoogle Scholar
  103. 103.
    Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ.Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 1993;75:229–240.PubMedCrossRefGoogle Scholar
  104. 104.
    Leveen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C. Mice deficient for PDGF-B show renal, cardiovascular, and hematological abnormalities. Genes Dev 1994;8:1875–1887.PubMedCrossRefGoogle Scholar
  105. 105.
    Soriano P. Abnormal kidney development and hematological disorders in PDGFβ-receptor mutant mice. Genes Dev 1994;8:1888–1896.PubMedCrossRefGoogle Scholar
  106. 106.
    Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T, Hogan BLM, Ichikawa I. Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 1995;96:2947–2954.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Matsusaka T, Nishimura H, Utsunomiya H, Kakuchi J, Niimura F, Inagami T, Fogo A, Ichikawa I. Chimeric mice carrying regional targeted deletion of the angiotensin type 1A receptor gene: evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells. J Clin Invest 1996;98:1867–1877.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Fine LG. Gene transfer into the kidney: promise for unraveling disease mechanisms, limitations for gene therapy. Kidney Int 1996;49:612–619.PubMedCrossRefGoogle Scholar
  109. 109.
    Riley DJ, Lee W-H. The potential of gene therapy for treatment of kidney diseases. Semin Nephrol 1995; 15:57–69.PubMedGoogle Scholar
  110. 110.
    Isaka Y, Brees DK, Ikegaya K, Kaneda Y, Imai E, Noble NA, Border WA. Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney. Nature Med 1996;2:418–423.PubMedCrossRefGoogle Scholar
  111. 111.
    Isaka Y, Akagi Y, Kaneda Y, Yamauchi A, Orita Y, Ueda N, Imai E. Gene therapy by TGF-β-receptor-IgG Fc chimera inhibited extracellular matrix accumulation in experimental glomerulonephritis. J Am Soc Nephrol 1996;7:1735 (abstr).Google Scholar
  112. 112.
    Akagi Y, Isaka Y, Ando Y, Kaneda Y, Ando A, Yamauch A, Ueda N, Imai E. Gene therapy by PDGF soluble receptor chimera suppressed progression of experimental glomerulonephritis through the inhibition of PDGF action. J Am Soc Nephrol 1996;7:1652 (abstr).Google Scholar
  113. 113.
    Zhu G, Nicholson AG, Sukhatme VP. Adenovirus-mediated β-galactosidase gene delivery to the liver leads to protein deposition in kidney glomeruli. J Am Soc Nephrol 1996;7:1751 (abstr).Google Scholar
  114. 114.
    Kashihara N, Maeshima Y, Sekikawa T, Okamoto K, Kanao K, Sugiyama H, Makino H, Ota Z, Yasuda T. Inhibition of human mesangial cell proliferation by decoy oligonucleotide targeting the transcription factor, NF-κB. J Am Soc Nephrol 1995;6:834 (abstr).Google Scholar
  115. 115.
    Morishita R, Tomita N, Gibbons GH, Tomita S, Zhang L, Kaneda Y, Ogihara T, Dzau VJ. Potential gene therapy for glomerulonephritis: transfection of NF-κB decoy inhibited TNF-α induced cytokines and adhesion molecules expression in vivo. J Am Soc Nephrol 1996;7:1711 (abstr).Google Scholar
  116. 116.
    Tomita N, Kim J, Gibbons GH, Baran D, Ogborn M, Stahl RAK, Tomita S, Zhang L, Kaneda Y, Dzau VJ. In vivo gene therapy of anti-Thy-1 nephritis using E2F decoy oligonucleotide. J Am Soc Nephrol 1995;6:887 (abstr).Google Scholar
  117. 117.
    Maeshima Y, Kashihara N, Sekikawa T, Okamoto K, Kanao K, Sugiyama H, Makino H, Ota Z, Yasuda T. Inhibition of mesangial cell proliferation in vitro and in vivo by decoy oligonucleotide which suppresses transcription factor E2F activity. J Am Soc Nephrol 1995;6:925 (abstr).Google Scholar
  118. 118.
    Tomosugi N, Yamaya S, Kimura K, Sakamoto K, Watanabe K, Takata M, Nakamura S, Sakamoto H, Ishii T, Nakazawa M, Asaka T, Yuri T, Ishikawa I. Antisense oligonucleotides for MCP-1 partially suppress glomerular macrophage infiltration in anti-GMB antibody nephritis. J Am Soc Nephrol 1996;7:1748 (abstr).Google Scholar
  119. 119.
    Fouqueray B, Suberville S, Isaka Y, Akagi Y, Gerard C, Velu T, Imai E, Baud L. Reduction of proteinuria in anti-glomerular basement membrane nephritis by interleukin-10 gene transfer. J Am Soc Nephrol 1996; 7:1698 (Abstr).Google Scholar
  120. 120.
    Kitamura M, Sütö TS. TGF-β and glomerulonephritis: anti-inflammatory versus prosclerotic actions. Nephrol Dial Transplant 1997;12:669–679.PubMedCrossRefGoogle Scholar
  121. 121.
    Munger K, Montreo A, Fukanaga M, Yura T, Badr K, In vivo transfection of human arachidonate 15-lipoxygenase into the rat kidney: evidence for suppression of leukotriene synthesis and for functional protection during accelerated nephrotoxic serum nephritis. J Am Soc Nephrol 1996;7:1649 (abstr).Google Scholar
  122. 122.
    Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature 1996;380:364–366.PubMedCrossRefGoogle Scholar
  123. 123.
    Schweinfest CW, Jorcyk CL, Fujiwara S, Papas TS. A heat-shock-inducible eukaryotic expression vector. Gene 1988;71:207–210.PubMedCrossRefGoogle Scholar
  124. 124.
    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.PubMedCrossRefGoogle Scholar
  125. 125.
    Israel DI, Kaufman RJ. Highly inducible expression from vectors containing multiple GREs in CHO cells overexpressing glucocorticoid receptor. Nucleic Acids Res 1989;17:4589–4604.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Totzke F, Marme D, Hug H. Inducible expression of human phospholipase C-γ2 and its activation by platelet-derived growth factor B-chain homodimer and platelet-derived growth factor A-chain homodimer in transfected NIH3T3 fibroblasts. Eur J Biochem 1992;203:633–639.PubMedCrossRefGoogle Scholar
  127. 127.
    Jones SN, Jones PG, Ibarguen H, Caskey CT, Craigen WJ. Induction of theCyp1a-1 dioxin-responsive enhancer in transgenic mice. Nucleic Acids Res 1991; 19:6547–6551.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Hallahan DE, Mauceri HJ, Seung LP, Dunphy EJ, Wayne JD, Hanna NN, Toledano A, Hellman S, Kufe DW, Weichselbaum RR. Spatial and temporal control of gene therapy using ionizing radiation. Nature Med 1995;1:786–791.PubMedCrossRefGoogle Scholar
  129. 129.
    Yarranton GT. Inducible vectors for expression in mammalian cells. Curr Opin Biotech 1992;3:506–511.PubMedCrossRefGoogle Scholar
  130. 130.
    Gossen M, Freundlieb S, Bander G Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science 1995;268:1766–1769.PubMedCrossRefGoogle Scholar
  131. 131.
    Gossen M, Bonin AL, Bujard H. Control of gene activity in higher eukaryotic cells by prokaryotic regulatory elements. Trends Biochem Sci. 1993;18:471–475.PubMedCrossRefGoogle Scholar
  132. 132.
    Fishman GI, Kaplan MA, Buttrick PM. Tetracycline-regulated cardiac gene expression in vivo. J Clin Invest 1994;93:1864–1868.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Passman RS, Fishman GI. Regulated expression of foreign genes in vivo after germline transfer. J Clin Invest 1994;94:2421–2425.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Schockett PE, Schatz DG. Diverse strategies for tetracycline-regulated inducible gene expression. Proc. Natl Acad Sci USA 1996;93:5173–5176.CrossRefGoogle Scholar
  135. 135.
    Delort JP, Capecchi MR. TAXI/UAS. A molecular switch to control expression of genes in vivo. Hum Gnee Ther 1996;7:809–820.CrossRefGoogle Scholar
  136. 136.
    No D, Yao T-P, Evans RM. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 1996;93:3346–3351.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Rivera VM, Clackson T, Natesan, S, Pollock R, Amara JF, Keenan T, Magari SR, Phillips T, Courage NL, Cerasoli F, Holt DA,Gilman M. A humanized system for pharmacologic control of gene expression. Nature Med 1996;2:1028–1032PubMedCrossRefGoogle Scholar
  138. 138.
    Varley AW, Coulthard MG, Meidell RS, Gerard RD, Munford RS. Inflammation-induced recombinant protein expression in vivo using promoters from acutephase protein genes. Proc. Natl Acad Sci USA 1995; 92:5346–5350.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Dusetti NJ, Vasseur S, Ortiz EM, Romeo, H, Dagorn J-C, Burrone O, Iovanna JL. The pancreatitis-associated protein I promoter allows targeting to the pancreas of a foreign gene, whose expression is up-regulated during pancreatic inflammation. J Biol Chem 1997;272:5800–5804.PubMedCrossRefGoogle Scholar
  140. 140.
    Thomas KR, Capecchi, MR. Site-directed mutagenesis by gen targeting in mouse embryo-derived stem cells. Cell 1987;51:503–512.PubMedCrossRefGoogle Scholar
  141. 141.
    Sauer B, Henderson N. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci USA 1988;85:5166–6170.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Rossant J, Nagy A. Genome engineering: the new mouse genetics. Nature Med 1995;1:592–594.PubMedCrossRefGoogle Scholar
  143. 143.
    Rajewsky K, Gu H, Kuhn R, Betz UAK, Muller W, Roes J, Schwenk F. Conditional gene targeting. J Clin Invest 1996;98:600–603.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K. Deletion of a DNA polymerase β gene segment in T cells using cell-type-specific gene targeting. Science 1994;265:103–106.PubMedCrossRefGoogle Scholar
  145. 145.
    Semenza GL, Koury ST, Nejfelt MK, Gearhart JD, Antonarakis SE. Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice. Proc Natl Acad Sci USA 1991;88:8725–8729.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Maxwell PH, Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ. Identification of the renal crythropoietin-producing cells using transgenic mice. Kidney Int 1993;44:1149–1162.PubMedCrossRefGoogle Scholar
  147. 147.
    Loya F, Yang Y, Lin C, Goldwasser E, Albitar M. Transgenic mice carrying the erythropoietin gene promoter linked tolacZ express the reporter in proximal convoluted tubule cells after hypoxia. Blood 1994; 84:1831–1836.PubMedGoogle Scholar
  148. 148.
    Harats D, Kurihara H, Belloni P, Oakley H, Ziober A, Ackley D, Cain G, Kurihara Y, Lawn R, Sigal E. Targeting gene expression to the vascular wall in transgenic mice using the murine preproendothelin-1 promoter. J Clin Invest 1995;95:1335–1344.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Sigmund CD, Jones CA, Fabian JR, Mullins JJ, Gross KW. Tissue and cell specific expression of a renin promoter-reporter gene construct in transgenic mice. Biochem Biophys Res Commun 1990; 170:344–350.PubMedCrossRefGoogle Scholar
  150. 150.
    Fukamizu A, Sugimura K, Takimoto E, Sugiyama F, Seo M-S, Takahashi S, Hatae T, Kajiwara N, Yagami K-I, Murakami K. Human renin in transgenic mouse kidney is localized to juxtaglomerular cells. Biochem J 1991;278:601–603.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    McKay R. Stem cells in the central nervous system. Science 1997;276:66–71.PubMedCrossRefGoogle Scholar
  152. 152.
    Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997;276:71–81.PubMedCrossRefGoogle Scholar

Copyright information

© CEN/CLJ 1997

Authors and Affiliations

  • Masanori Kitamura
    • 1
  1. 1.Glomerular Bioengineering Unit, Department of MedicineUniversity College London Medical School, The Rayne InstituteLondonUK

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