title: Mutation within the hinge region of the transcription factor Nr2f2 attenuates salt-sensitive hypertension.
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 Nr2f2(mutant) 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 Nr2f2(mutant) 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.
authors: 1] Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [2] Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA.
authors: Sivarajan
authors: S
authors: Kumarasamy
authors: 1] Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [2] Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA.
authors: Harshal
authors: H
authors: Waghulde
authors: 1] Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [2] Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA.
authors: Kathirvel
authors: K
authors: Gopalakrishnan
authors: 1] Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [2] Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA.
authors: Blair
authors: B
authors: Mell
authors: 1] Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [2] Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [3] Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA.
authors: Eric
authors: E
authors: Morgan
authors: 1] Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA [2] Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio 43614-2598, USA.
authors: Bina
authors: B
authors: Joe
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D019556:COS Cells; D051837:COUP Transcription Factor II / Q000235:genetics* / Q000502:physiology*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D003971:Diastole; D004195:Disease Models, Animal; D000075222:Essential Hypertension; D005091:Exons; D005260:Female; D017353:Gene Deletion; D055106:Genome-Wide Association Study; D006973:Hypertension / Q000235:genetics*; D008297:Male; D009154:Mutation; D025941:Protein Interaction Mapping; D051381:Rats; D013599:Systole; D014157:Transcription Factors / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D051837:COUP Transcription Factor II; D004268:DNA-Binding Proteins; C497588:Nr2f2 protein, rat; D014157:Transcription Factors; C000605754:Zfpm2 protein, rat