Hypervolemic hypertension in mice with systemic inactivation of the (floxed) guanylyl cyclase-A gene by alphaMHC-Cre-mediated recombination

Boris V Skryabin, Rita Holtwick, Larissa Fabritz, Markus N Kruse, Ilka Veltrup, Jörg Stypmann, Paulus Kirchhof, Karim Sabrane, Alexander Bubikat, Melanie Voss, Michaela Kuhn

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


To dissect the tissue-specific functions of atrial natriuretic peptide (ANP), we recently introduced loxP sites into the murine gene for its receptor, guanylyl cyclase-A (GC-A), by homologous recombination (tri-lox GC-A). For either smooth-muscle or cardiomyocyte-restricted deletion of GC-A, floxed GC-A mice were mated to transgenic mice expressing Cre-recombinase under the control of the smooth-muscle SM22 or the cardiac alphaMHC promoter. As shown in these studies, Cre-mediated recombination of the floxed GC-A gene fully inactivated GC-A function in a cell-restricted manner. In the present study we show that alphaMHC-Cre, but not SM22-Cre, with high frequency generates genomic recombinations of the floxed GC-A gene segments which were transmitted to the germline. Alleles with partial or complete deletions were readily recovered from the next generation, after segregation of the Cre-transgene. We took advantage of this strategy to generate a new mouse line with global, systemic deletion of GC-A. Doppler-echocardiographic and physiological studies in these mice demonstrate for the first time the tremendous impact of ANP/GC-A dysfunction on chronic blood volume homeostasis.

Original languageEnglish
Pages (from-to)288-98
Number of pages11
Issue number4
Publication statusPublished - Aug 2004


  • Animals
  • Atrial Natriuretic Factor
  • Blood Pressure
  • Blood Volume
  • Blotting, Southern
  • DNA Primers
  • Echocardiography, Doppler
  • Gene Components
  • Gene Silencing
  • Guanylate Cyclase
  • Heart
  • Hypertension
  • Integrases
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins
  • Models, Animal
  • Muscle Proteins
  • Muscle, Smooth
  • Myosin Heavy Chains
  • Promoter Regions, Genetic
  • Receptors, Atrial Natriuretic Factor
  • Reverse Transcriptase Polymerase Chain Reaction


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