Hypertension is the leading risk factor for cardiovascular disease and impacts one in three adults globally. One genetic mechanism that may affect blood pressure regulation and alter hypertension risk in the general population is the disruption of chromatin conformation by common genetic variation. CCCTCF-binding factor (CTCF) has many important functions including regulating the conformation of chromatin by binding to specific DNA sequences and can thereby alter gene expression. The renin locus has multiple CTCF motifs surrounding the renin gene and cellular expression of CTCF is critical for proper renin expression. Despite these important functions, the role that local chromatin conformation plays to regulate normal renin expression including its response to stimuli such as dietary salt intake and in the downstream regulation of blood pressure is unknown. We hypothesize that disruption of local chromatin conformation can alter gene expression, intermediate physiological mechanisms, and blood pressure. A mutant rat model was created using CRISPR-Cas9 in the genetic background of the Dahl salt-sensitive (SS) rat with a disruption to the CTCF binding motif located within an intron of Golt1a near the Ren gene which we have previously demonstrated an interaction with the renin proximal promoter. Here we report the preliminary characterization of this model for renin expression and plasma renin activity (PRA). Chromatin immunoprecipitation-qPCR showed a reduction in CTCF binding at the Golt1a locus in our mutant model compared to wild-type (WT), confirming our mutation resulted in a disruption in CTCF binding in vivo. An expected reduction (p<0.05) in renin expression was found in male and female WT and mutant rats in response to a high salt diet. WT males showed an expected inverse PRA relationship to dietary salt (WT: 0.1% NaCl=17.52, 0.4% NaCl=12.87, 4.0% NaCl=7.13; p<0.05) however, interestingly, mutant males failed to increase PRA in response to very low salt (0.1% NaCl) challenge (0.1% NaCl mutant=13.87; p<0.05 compared to WT 0.1% NaCl). Female mutants showed a similar but non-significant trend. Taken together, these data suggest that the disruption of CTCF binding in a region which interacts with the renin proximal promoter can alter renin expression and the plasma renin activity in response to very low dietary salt in SS rats. NIH 5P01HL149620-03 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.