Skip to main content

Advertisement

SpringerLink
Log in

Transgenic mice and their impact on kidney research

  • Transport Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The kidney is a key organ in the maintenance of ion and fluid homeostasis and specific transport systems localized along the nephron guarantee this function. Due to its large functional heterogeneity, experiments on the whole organ level cannot be easily performed, and thus more refined tools are needed, like for example the development of specific recombination systems to gain knowledge on the physiological role of single proteins implicated in ion transport. This review introduces the transgenic technology developed over the past decades, and then focuses on recent strategies for generating kidney-specific gene targeting, over-expression, and gene ablation in mice, that will help to understand the physiological role of proteins implicated in salt and water balance in the kidney.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ahn D, Ge Y, Stricklett PK, Gill P, Taylor D, Hughes AK, Yanagisawa M, Miller L, Nelson RD, Kohan DE (2004) Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention. J Clin Invest 114:504–511

    PubMed  CAS  Google Scholar 

  2. Aigner B, Fleischmann M, Muller M, Brem G (1999) Stable long-term germ-line transmission of transgene integration sites in mice. Transgenic Res 8:1–8

    PubMed  CAS  Google Scholar 

  3. Bachmann S, Schlichting U, Geist B, Mutig K, Petsch T, Bacic D, Wagner CA, Kaissling B, Biber J, Murer H, Willnow TE (2004) Kidney-specific inactivation of the megalin gene impairs trafficking of renal inorganic sodium phosphate cotransporter (NaPi-IIa). J Am Soc Nephrol 15:892–900

    PubMed  CAS  Google Scholar 

  4. Barker PM, Ngugen MS, Gatzy JT, Grubb B, Norman H, Hummler E, Rossier B, Boucher RC, Koller B (1998) Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice: insights into perinatal adaptation and pseudohypoaldosteronism. J Clin Invest 102:1634–1640

    PubMed  CAS  Google Scholar 

  5. Beermann F, Hummler E, Franke U, Hansmann I (1988) Allocation of a transgenic c-myc integration site to mouse chromosome 8B3-C1. Cytogenet Cell Genet 49:311–312

    PubMed  CAS  Google Scholar 

  6. Beermann F, Jenderny J, Hummler E, Hansmann I (1987) Inheritance of a meiosis I error expressed in mouse oocytes and modulated by a maternal factor. Genet Res 49:239–243

    Article  PubMed  CAS  Google Scholar 

  7. Bouchard M, Souabni A, Busslinger M (2004) Tissue-specific expression of cre recombinase from the Pax8 locus. Genesis 38:105–109

    PubMed  CAS  Google Scholar 

  8. Bradley A, Liu P (1996) Target practice in transgenics. Nat Genet 14:121–123

    PubMed  CAS  Google Scholar 

  9. Brinster R, Allen J, Behringer R, Gelinas R, Palmiter R (1988) Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A 85:836–840

    PubMed  CAS  Google Scholar 

  10. Brinster R, Chen H, Trumbauer M, Senear A, Warren R, Palmiter R (1981) Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27:223–231

    PubMed  CAS  Google Scholar 

  11. Buchholz F, Refaeli Y, Trumpp A, Bishop JM (2000) Inducible chromosomal translocation of AML1 and ETO genes through Cre/loxP-mediated recombination in the mouse. EMBO Rep 1:133–139

    PubMed  CAS  Google Scholar 

  12. Chang CT, Bens M, Hummler E, Boulkroun S, Schild L, Teulon J, Rossier BC, Vandewalle A (2005) Vasopressin-stimulated CFTR Cl-currents are increased in the renal collecting duct cells of a mouse model of Liddle’s syndrome. J Physiol 562:271–284

    PubMed  CAS  Google Scholar 

  13. Dahlmann A, Pradervand S, Hummler E, Rossier BC, Frindt G, Palmer LG (2003) Mineralocorticoid regulation of epithelial Na + channels is maintained in a mouse model of Liddle’s syndrome. Am J Physiol Renal Physiol 285:F310–F318

    PubMed  CAS  Google Scholar 

  14. Di-Poi N, Zakany J, Duboule D (2007) Distinct roles and regulation for Hoxd genes in metanephric kidney development. PLoS Genet 3:2500–2514

    CAS  Google Scholar 

  15. Ding Y, Davisson RL, Hardy DO, Zhu LJ, Merrill DC, Catterall JF, Sigmund CD (1997) The kidney androgen-regulated protein promoter confers renal proximal tubule cell-specific and highly androgen-responsive expression on the human angiotensinogen gene in transgenic mice. J Biol Chem 272:28142–28148

    PubMed  CAS  Google Scholar 

  16. Dworniczak B, Skryabin B, Tchinda J, Heuck S, Seesing FJ, Metzger D, Chambon P, Horst J, Pennekamp P (2007) Inducible Cre/loxP recombination in the mouse proximal tubule. Nephron Exp Nephrol 106:e11–e20

    PubMed  CAS  Google Scholar 

  17. Eremina V, Wong M, Cui S, Schwartz L, Quaggin S (2002) Glomerular-specific gene excision in vivo. J Am Soc Nephrol 13:788–793

    PubMed  CAS  Google Scholar 

  18. Evans M, Kaufman M (1981) Establishment in culture of pluripotent cells from mouse embryos. Nature 292:154–156

    PubMed  CAS  Google Scholar 

  19. Ge Y, Ahn D, Stricklett PK, Hughes AK, Yanagisawa M, Verbalis JG, Kohan DE (2005) Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. Am J Physiol Renal Physiol 288:F912–F920

    PubMed  CAS  Google Scholar 

  20. Ge Y, Bagnall A, Stricklett PK, Strait K, Webb DJ, Kotelevtsev Y, Kohan DE (2006) Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol Renal Physiol 291:F1274–F1280

    PubMed  CAS  Google Scholar 

  21. Ge Y, Strait KA, Stricklett PK, Yang T, Kohan DE (2007) Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion. Am J Physiol Renal Physiol 293:F1805–F1810

    PubMed  CAS  Google Scholar 

  22. Ge Y, Stricklett PK, Hughes AK, Yanagisawa M, Kohan DE (2005) Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure. Am J Physiol Renal Physiol 289:F692–F698

    PubMed  CAS  Google Scholar 

  23. Giraldo P, Montoliu L (2001) Size matters: use of YACs, BACs and PACs in transgenic animals. Transgenic Res 10:83–103

    PubMed  CAS  Google Scholar 

  24. Gordon J, Scangos G, Plotkin D, Barbosa J, Ruddle F (1980) Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci U S A 77:7380–7384

    PubMed  CAS  Google Scholar 

  25. Gossler A, Doetschman T, Korn R, Serfling E, Kemler R (1986) Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc Natl Acad Sci U S A 83:9065–9069

    PubMed  CAS  Google Scholar 

  26. Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K (1994) Deletion of a DNA polymerase ß gene segment in T cells using cell type-specific gene targeting. Science 265:103–106

    PubMed  CAS  Google Scholar 

  27. Gu H, Zou Y, Rajewsky K (1993) Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP mediated gene targeting. Cell 73:1155–1164

    PubMed  CAS  Google Scholar 

  28. Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, Magnuson MA, Redha R, Zhang Y, Breyer MD (2005) Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med 11:861–866

    PubMed  CAS  Google Scholar 

  29. Guo DF, Chenier I, Lavoie JL, Chan JS, Hamet P, Tremblay J, Chen XM, Wang DH, Inagami T (2006) Development of hypertension and kidney hypertrophy in transgenic mice overexpressing ARAP1 gene in the kidney. Hypertension 48:453–459

    PubMed  CAS  Google Scholar 

  30. Guyonneau L, Rossier A, Richard C, Hummler E, Beermann F (2002) Expression of Cre recombinase in pigment cells. Pigment Cell Res 15:305–309

    PubMed  CAS  Google Scholar 

  31. Hiesberger T, Bai Y, Shao X, McNally BT, Sinclair AM, Tian X, Somlo S, Igarashi P (2004) Mutation of hepatocyte nuclear factor-1beta inhibits Pkhd1 gene expression and produces renal cysts in mice. J Clin Invest 113:814–825

    PubMed  CAS  Google Scholar 

  32. Higgins D, Kimura K, Bernhardt W, Shrimanker N, Akai Y, Hohenstein B, Saito Y, Johnson R, Kretzler M, COhen C, Eckardt K, Iwano M, Haase V (2007) Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest 117:3810–3820

    PubMed  CAS  Google Scholar 

  33. Hummler E (1999) Implication of ENaC in salt-sensitive hypertension. J Steroid Biochem Mol Biol 69:385–390

    PubMed  CAS  Google Scholar 

  34. Hummler E (2003) Epithelial sodium channel, salt intake, and hypertension. Curr Hypertens Rep 5:11–18

    PubMed  Google Scholar 

  35. Hummler E, Barker P, Gatzy J, Beermann F, Verdumo C, Schmidt A, Boucher R, Rossier B (1996) Early death due to defective neonatal lung liquid clearance in aENaC-deficient mice. Nat Genet 12:325–328

    PubMed  CAS  Google Scholar 

  36. Hummler E, Barker P, Talbot C, Wang Q, Verdumo C, Grubb B, Gatzy J, Burnier M, Horisberger J-D, Beermann F, Boucher R, Rossier BC (1997) A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism. Proc Natl Acad Sci USA 94:11710–11715

    PubMed  CAS  Google Scholar 

  37. Hummler E, Beermann F (2000) Scnn1 sodium channel gene family in genetically engineered mice. J Am Soc Nephrol 11(Suppl 16):S129–S134

    PubMed  CAS  Google Scholar 

  38. Hummler E, Mérillat AM, Rubera I, Rossier BC, Beermann F (2002) Conditional gene targeting of the Scnn1a (aENaC) gene locus. Genesis 32:169–172

    PubMed  CAS  Google Scholar 

  39. Hummler E, Vallon V (2005) Lessons from mouse mutants of epithelial sodium channel and its regulatory proteins. J Am Soc Nephrol 16:3160–3166

    PubMed  CAS  Google Scholar 

  40. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG (2002) Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 110:341–350

    PubMed  CAS  Google Scholar 

  41. Jaenisch R (1976) Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus. Proc Natl Acad Sci U S A 73:1260–1264

    PubMed  CAS  Google Scholar 

  42. Jaenisch R (1988) Transgenic animals. Science 240:1468–1474

    PubMed  CAS  Google Scholar 

  43. Jaenisch R, Mintz B (1974) Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Proc Natl Acad Sci U S A 71:1250–1254

    PubMed  CAS  Google Scholar 

  44. Kim D, Wang M, Cai Q, Brooks H, Dressler GR (2007) Pax transactivation-domain interacting protein is required for urine concentration and osmotolerance in collecting duct epithelia. J Am Soc Nephrol 18:1458–1465

    PubMed  CAS  Google Scholar 

  45. Kwan K (2002) Conditional alleles in mice: practical considerations for tissue-specific knock-outs. Genesis 32:49–62

    PubMed  CAS  Google Scholar 

  46. Lam AK, Ko BC, Tam S, Morris R, Yang JY, Chung SK, Chung SS (2004) Osmotic response element-binding protein (OREBP) is an essential regulator of the urine concentrating mechanism. J Biol Chem 279:48048–48054

    PubMed  CAS  Google Scholar 

  47. Lan Y, Wang Q, Ovitt C, Jiang R (2007) A unique mouse strain expressing Cre recombinase for tissue-specific analysis of gene function in palate and kidney development. Genesis 45:618–624

    PubMed  CAS  Google Scholar 

  48. Lantinga-van Leeuwen I, Leonhard W, van der Wal A, Breuning M, de Heer E, Peters D (2007) Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet 16:3188–3196

    PubMed  CAS  Google Scholar 

  49. Lantinga-van Leeuwen IS, Leonhard WN, van de Wal A, Breuning MH, Verbeek S, de Heer E, Peters DJ (2006) Transgenic mice expressing tamoxifen-inducible Cre for somatic gene modification in renal epithelial cells. Genesis 44:225–232

    PubMed  CAS  Google Scholar 

  50. Larue L, Beermann F (2007) Cutaneous melanoma in genetically modified animals. Pigment Cell Res 20:485–497

    PubMed  CAS  Google Scholar 

  51. Lavoie JL, Lake-Bruse KD, Sigmund CD (2004) Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule. Am J Physiol Renal Physiol 286:F965–F971

    PubMed  CAS  Google Scholar 

  52. Leheste JR, Melsen F, Wellner M, Jansen P, Schlichting U, Renner-Muller I, Andreassen TT, Wolf E, Bachmann S, Nykjaer A, Willnow TE (2003) Hypocalcemia and osteopathy in mice with kidney-specific megalin gene defect. FASEB J 17:247–249

    PubMed  CAS  Google Scholar 

  53. Li H, Zhou X, Davis DR, Xu D, Sigmund CD (2008) An androgen-inducible proximal tubule-specific cre-recombinase transgenic model. Am J Physiol Renal Physiol 294:F1481–F1486

    PubMed  CAS  Google Scholar 

  54. Lo C (1986) Localization of low abundance DNA sequences in tissue sections by in situ hybridization. J Cell Sci 81:143–162

    PubMed  CAS  Google Scholar 

  55. Lois C, Hong E, Pease S, Brown E, Baltimore D (2002) Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295:868–872

    PubMed  CAS  Google Scholar 

  56. Mak T (2007) Gene targeting in embryonic stem cells scores a knockout in Stockholm. Cell 131:1027–1031

    PubMed  CAS  Google Scholar 

  57. Malynn B, de Alboran I, O’Hagan R, Bronson R, Davidson L, DePinho R, Alt F (2000) N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation. Genes Dev 14:1390–1399

    PubMed  CAS  Google Scholar 

  58. Martin G (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638

    PubMed  CAS  Google Scholar 

  59. McDonald FJ, Yang B, Hrstka RF, Drummond HA, Tarr DE, McCray PB, Stokes JB, Welsh MJ, Williamson RA (1999) Disruption of the beta subunit of the epithelial Na + channel in mice: hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype. Proc Natl Acad Sci U S A 96:1727–1731

    PubMed  CAS  Google Scholar 

  60. Metzger D, Clifford J, Chiba H, Chambon P (1995) Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase. Proc Natl Acad Sci U S A 92:6991–6995

    PubMed  CAS  Google Scholar 

  61. Moeller M, Sanden S, Soofi A, Wiggins R, Holzman L (2003) Podocyte-specific expression of Cre recombinase in transgenic mice. Genesis 35:39–42

    PubMed  CAS  Google Scholar 

  62. Mossbrugger I, Hoelzlwimmer G, Calzada-Wack J, Quintanilla-Martinez L (2007) Standardized morphological phenotyping of mouse models of human diseases within the German Mouse Clinic. Verh Dtsch Ges Pathol 91:98–103

    PubMed  CAS  Google Scholar 

  63. Murisier F, Aydin I, Guichard S, Brunschwiler S, Beermann F (2008) Expression from a bacterial artificial chromosome containing the Dct gene locus. Pigment Cell Mel Res 21:212–215

    CAS  Google Scholar 

  64. Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26:99–109

    PubMed  CAS  Google Scholar 

  65. Nagy A, Gertsenstein M, Vintersten K, Behringer R (2003) Manipulating the mouse embryo — a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  66. Naray-Fejes-Toth A, Fejes-Toth G (2007) Novel mouse strain with Cre recombinase in 11beta-hydroxysteroid dehydrogenase-2-expressing cells. Am J Physiol Renal Physiol 292:F486–F494

    PubMed  CAS  Google Scholar 

  67. Nelson RD, Stricklett P, Gustafson C, Stevens A, Ausiello D, Brown D, Kohan DE (1998) Expression of an AQP2 Cre recombinase transgene in kidney and male reproductive system of transgenic mice. Am J Physiol 275:C216–C226

    PubMed  CAS  Google Scholar 

  68. Ohyama T, Groves A (2004) Generation of Pax2-Cre mice by modification of a Pax2 bacterial artificial chromosome. Genesis 38:195–199

    PubMed  CAS  Google Scholar 

  69. Palmiter R, Brinster R (1986) Germ-line transformation of mice. Annu Rev Genet 20:465–499

    PubMed  CAS  Google Scholar 

  70. Patel C, Wyne K, McGuire D (2005) Thiazolidenediones, peripheral oedema and congestive heart failure: what is the evidence? Diab Vasc Dis Res 2:61–66

    PubMed  Google Scholar 

  71. Patel V, Li L, Cobo-Stark P, Shao X, Somlo S, Lin F, Igarashi P (2008) Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia. Hum Mol Genet 17:1578–1590

    PubMed  CAS  Google Scholar 

  72. Pfeifer A (2004) Lentiviral transgenesis. Transgenic Res 13:513–522

    PubMed  CAS  Google Scholar 

  73. Porret A, Mérillat A, Guichard S, Beermann F, Hummler E (2006) Tissue-specific transgenic and knockout mice. Meth Mol Biol 337:185–205

    CAS  Google Scholar 

  74. Pradervand S, Barker P, Wang Q, Ernst SA, Beermann F, Grubb B, Burnier M, Schmidt A, Bindels RJM, Gatzy J, Rossier BC, Hummler E (1999) Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel. Proc Natl Acad Sci U S A 96:1732–1737

    PubMed  CAS  Google Scholar 

  75. Pradervand S, Vandewalle A, Bens M, Gautschi I, Loffing J, Hummler E, Schild L, Rossier BC (2003) Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. J Am Soc Nephrol 14:2219–2228

    PubMed  CAS  Google Scholar 

  76. Pradervand S, Wang Q, Burnier M, Beermann F, Horisberger J-D, Hummler E, Rossier B (1999) A mouse model for Liddle’s syndrome. J Am Soc Nephrol 10:2527–2533

    PubMed  CAS  Google Scholar 

  77. Praetorius J, Fenton R, Füechtbauer E, Hofmeister M (2008) TRPV5-promoter driven expression of EGFP produces fluorescence in late DCT, CNT and early CCD. FASEB J 22:1159.16

    Google Scholar 

  78. Rachel R, Wellington S, Warburton D, Mason C, Beermann F (2002) A new allele of Gli3 and a new mutation, circletail (Crc), resulting from a single transgenic experiment. Genesis 33:55–61

    PubMed  CAS  Google Scholar 

  79. Rankin EB, Tomaszewski JE, Haase VH (2006) Renal cyst development in mice with conditional inactivation of the von Hippel–Lindau tumor suppressor. Cancer Res 66:2576–2583

    PubMed  CAS  Google Scholar 

  80. Raoul C, Abbas-Terki T, Bensadoun J, Guillot S, Haase G, Szule J, Henderson C, Aebischer P (2005) Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nature Med 11:423–428

    PubMed  CAS  Google Scholar 

  81. Rodriguez C, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, Stewart A, Dymecki S (2000) High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25:139–140

    PubMed  CAS  Google Scholar 

  82. Rojek A, Fuchtbauer EM, Kwon TH, Frokiaer J, Nielsen S (2006) Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proc Natl Acad Sci U S A 103:6037–6042

    PubMed  CAS  Google Scholar 

  83. Ronzaud C, Loffing J, Bleich M, Gretz N, Grone HJ, Schutz G, Berger S (2007) Impairment of sodium balance in mice deficient in renal principal cell mineralocorticoid receptor. J Am Soc Nephrol 18:1679–1687

    PubMed  CAS  Google Scholar 

  84. Rossetti D, Chauveau D, Walker D, Saggar-Malik A, Winearls C, Torres V, Harris P (2002) A complete mutation screen of the ADPKD genes by DHPLC. Kidney Int 61:1588–1599

    PubMed  CAS  Google Scholar 

  85. Rubera I, Loffing J, Palmer LG, Frindt G, Fowler-Jaeger N, Sauter D, Carroll T, McMahon A, Hummler E, Rossier BC (2003) Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance. J Clin Invest 112:554–565

    PubMed  CAS  Google Scholar 

  86. Rubera I, Poujeol C, Bertin G, Hasseine L, Counillon L, Poujeol P, Tauc M (2004) Specific Cre/Lox recombination in the mouse proximal tubule. J Am Soc Nephrol 15:2050–2056

    PubMed  CAS  Google Scholar 

  87. Sachetelli S, Liu Q, Zhang SL, Liu F, Hsieh TJ, Brezniceanu ML, Guo DF, Filep JG, Ingelfinger JR, Sigmund CD, Hamet P, Chan JS (2006) RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney. Kidney Int 69:1016–1023

    PubMed  CAS  Google Scholar 

  88. Sauer B (1993) Manipulation of transgenes by site-specific recombination: use of Cre recombinase. Methods Enzymol 225:890–900

    PubMed  CAS  Google Scholar 

  89. Sauvain M, Dorr A, Stevenson B, Quazzoloa A, Naef F, Wiznerowicz M, Schütz F, Jongeneel V, Duboule D, Spitz F, Trono D (2008) Genotypic features of lentiviral transgenic mice. J Virol 82:7111–7119

    PubMed  CAS  Google Scholar 

  90. Scangos G, Bieberich C (1987) Gene transfer into mice. Adv Genet 24:285–322

    PubMed  CAS  Google Scholar 

  91. Schneider MP, Ge Y, Pollock DM, Pollock JS, Kohan DE (2008) Collecting duct-derived endothelin regulates arterial pressure and Na excretion via nitric oxide. Hypertension 51:1605–1610

    PubMed  CAS  Google Scholar 

  92. Schönig K, Schwenk F, Rajewsky K, Bujard H (2002) Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res 30:e134

    PubMed  Google Scholar 

  93. Schwartzberg P, Goff S, Robertson E (1989) Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. Science 246:799–803

    PubMed  CAS  Google Scholar 

  94. Scott B, Lois C (2005) Generation of tissue-specific transgenic birds with lentiviral vectors. Proc Natl Acad Sci U S A 102:16443–16447

    PubMed  CAS  Google Scholar 

  95. Sequeira Lopez M, Pentz E, Nomasa T, Smithies O, Gomez R (2004) Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened. Dev Cell 6:719–728

    PubMed  Google Scholar 

  96. Shao X, Somlo S, Igarashi P (2002) Epithelial-specific Cre/lox recombination in the developing kidney and genitourinary tract. J Am Soc Nephrol 13:1837–1846

    PubMed  CAS  Google Scholar 

  97. Simpson E, Linder C, Sargent E, Davisson M, Mobraaten L, Sharp J (1997) Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice. Nat Genet 16:19–27

    PubMed  CAS  Google Scholar 

  98. Smith AJH, De Sousa MA, Kwabi-Addo B, Heppell-Parton A, Impey H, Rabbitts P (1995) A site-directed chromosomal translocation induced in embryonic stem cells by Cre-loxP recombination. Nat Genet 9:376–385

    PubMed  CAS  Google Scholar 

  99. Soriano P (1999) Genaralized lacZ expression with the ROSA26Cre reporter strain. Nat Genet 21:70–71

    PubMed  CAS  Google Scholar 

  100. Stricklett PK, Taylor D, Nelson RD, Kohan DE (2003) Thick ascending limb-specific expression of Cre recombinase. Am J Physiol Renal Physiol 285:F33–F39

    PubMed  CAS  Google Scholar 

  101. Szule J, Wiznerowicz M, Sauvain M, Trono D, Aebischer P (2006) A versatile tool for conditional gene expression and knockdown. Nature Methods 3:109–116

    Google Scholar 

  102. Taketo M, Schroeder A, Mobraaten L, Gunning K, Hanten G, Fox R, Roderick T, Stewart C, Lilly F, Hansen C, Overbeek P (1991) FVB/N: An inbred mouse strain preferable for transgenic analyses. Proc Natl Acad Sci U S A 88:2065–2069

    PubMed  CAS  Google Scholar 

  103. Thivierge C, Kurbegovic A, Couillard M, Guillaume R, Cote O, Trudel M (2006) Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol 26:1538–1548

    PubMed  CAS  Google Scholar 

  104. Thomas K, Folger K, Capecchi MR (1986) High frequency targeting of genes to specific sites in the mammalian genome. Cell 44:419–428

    PubMed  CAS  Google Scholar 

  105. Thompson S, Clarke A, Pow A, Hooper M, Melton D (1989) Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell 56:313–321

    PubMed  CAS  Google Scholar 

  106. Threadgill D, Yee D, Matin A, Nadeau J, Magnuson T (1997) Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain. Mamm Genome 8:390–393

    PubMed  CAS  Google Scholar 

  107. Tiwari S, Sharma N, Gill PS, Igarashi P, Kahn CR, Wade JB, Ecelbarger CM (2008) Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor. Proc Natl Acad Sci U S A 105:6469–6474

    PubMed  CAS  Google Scholar 

  108. Traykova-Brauch M, Schonig K, Greiner O, Miloud T, Jauch A, Bode M, Felsher D, Glick A, Kwiatkowski D, Bujard H, Horst J, von Knebel Doeberitz M, Niggli F, Kriz W, Grone H, Koesters R (2008) An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nat Med 14:985–921

    Google Scholar 

  109. Vincent S, Robertson E (2004) Targeted insertion of an IRES Cre into the Hnf4a locus: Cre-mediated recombination in the liver, kidney, and gut epithelium. Genesis 39:206–211

    PubMed  CAS  Google Scholar 

  110. Wagner E, Stewart T, Mintz B (1981) The human ß-globin gene and a functional thymidine kinase gene in developing mice. Proc Natl Acad Sci U S A 78:5016–5020

    PubMed  CAS  Google Scholar 

  111. Wang Q, Clement S, Gabbiani G, Horisberger J-D, Burnier M, Rossier BC, Hummler E (2004) Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under a normal salt-diet. Am J Physiol Renal Physiol 286:F1178–F1184

    PubMed  CAS  Google Scholar 

  112. Yang JY, Tam WY, Tam S, Guo H, Wu X, Li G, Chau JF, Klein JD, Chung SK, Sands JM, Chung SS (2006) Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism. Am J Physiol Renal Physiol 291:F186–F195

    PubMed  CAS  Google Scholar 

  113. Yu J, Carroll TJ, McMahon AP (2002) Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney. Development 129:5301–5312

    PubMed  CAS  Google Scholar 

  114. Zachgo J, Gossler A (1993) Gene and enhancer trap screens in ES cell chimeras. In: Joyner A (ed) Gene targeting a practical approach. IRL, Oxford, pp 181–227

    Google Scholar 

  115. Zbikowska HM, Soukhareva N, Behnam R, Chang R, Drews R, Lubon H, Hammond D, Soukharev S (2002) The use of the uromodulin promoter to target production of recombinant proteins into urine of transgenic animals. Transgenic Res 11:425–435

    PubMed  CAS  Google Scholar 

  116. Zbikowska HM, Soukhareva N, Behnam R, Lubon H, Hammond D, Soukharev S (2002) Uromodulin promoter directs high-level expression of biologically active human alpha1-antitrypsin into mouse urine. Biochem J 365:7–11

    PubMed  CAS  Google Scholar 

  117. Zhang H, Zhang A, Kohan DE, Nelson RD, Gonzalez FJ, Yang T (2005) Collecting duct-specific deletion of peroxisome proliferator-activated receptor gamma blocks thiazolidinedione-induced fluid retention. Proc Natl Acad Sci U S A 102:9406–9411

    PubMed  CAS  Google Scholar 

  118. Zhao H, Kegg H, Grady S, Truong HT, Robinson ML, Baum M, Bates CM (2004) Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol 276:403–415

    PubMed  CAS  Google Scholar 

  119. Zhu X, Cheng J, Huang L, Gao J, Zhang ZT, Pak J, Wu XR (2003) Renal tubule-specific expression and urinary secretion of human growth hormone: a kidney-based transgenic bioreactor growth. Transgenic Res 12:155–162

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Work in the laboratory of FB is supported by grants from The Swiss National Science Foundation and The Swiss Cancer League. Work in the laboratory of EH is supported by a grant from the Swiss National Science Foundation.

Author information

Authors and Affiliations

  1. CNRS-FRE 3093, Université de Nice Sophia-Antipolis, 06108, Nice Cedex 2, France

    Isabelle Rubera

  2. Département de Pharmacologie et de Toxicologie, University of Lausanne, Rue du Bugnon 27, CH-1005, Lausanne, Switzerland

    Edith Hummler

  3. Transgenic Animal Facility (TAF), University of Lausanne and University Hospitals, Rue du Bugnon 27, 1005, Lausanne, Switzerland

    Edith Hummler

  4. ISREC (Swiss Institute for Experimental Cancer Research), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Ch. des Boveresses 155, 1066, Epalinges, Switzerland

    Friedrich Beermann

Authors
  1. Isabelle Rubera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edith Hummler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Friedrich Beermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edith Hummler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rubera, I., Hummler, E. & Beermann, F. Transgenic mice and their impact on kidney research. Pflugers Arch - Eur J Physiol 458, 211–222 (2009). https://doi.org/10.1007/s00424-008-0624-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-008-0624-0

Keywords

Search

Navigation