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Mutation within the hinge region of the transcription factor Nr2f2 attenuates salt-sensitive hypertension

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  • Sivarajan Kumarasamy

    (Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences
    University of Toledo College of Medicine and Life Sciences)

  • Harshal Waghulde

    (Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences
    University of Toledo College of Medicine and Life Sciences)

  • Kathirvel Gopalakrishnan

    (Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences
    University of Toledo College of Medicine and Life Sciences)

  • Blair Mell

    (Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences
    University of Toledo College of Medicine and Life Sciences)

  • Eric Morgan

    (Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences
    University of Toledo College of Medicine and Life Sciences
    Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences)

  • Bina Joe

    (Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences
    University of Toledo College of Medicine and Life Sciences)

Abstract

Genome-wide association studies (GWAS) have prioritized a transcription factor, nuclear receptor 2 family 2 (NR2F2), as being associated with essential hypertension in humans. Here we provide evidence that validates this association and indicates that Nr2f2 is a genetic determinant of blood pressure (BP). Using the zinc-finger nuclease technology, the generation of a targeted Nr2f2-edited rat model is reported. The resulting gene-edited rats have a 15 bp deletion in exon 2 leading to a five-amino-acid deletion in the hinge region of the mutant Nr2f2 protein. Both systolic and diastolic blood pressures of the Nr2f2mutant rats are significantly lower than controls. Because the hinge region of Nr2f2 is required for interaction with Friend of Gata2 (Fog2), protein–protein interaction is examined. Interaction of Nr2f2mutant protein with Fog2 is greater than that with the wild-type Nr2f2, indicating that the extent of interaction between these two transcription factors critically influences BP.

Suggested Citation

  • Sivarajan Kumarasamy & Harshal Waghulde & Kathirvel Gopalakrishnan & Blair Mell & Eric Morgan & Bina Joe, 2015. "Mutation within the hinge region of the transcription factor Nr2f2 attenuates salt-sensitive hypertension," Nature Communications, Nature, vol. 6(1), pages 1-7, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7252
    DOI: 10.1038/ncomms7252
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