Abstract 16: Physiological Characterization of a Selective Knockout of the Intracellular Isoform of Renin in the Brain of Mice

• DOI: 10.1161/hyp.62.suppl_1.a16
• Publication Date: 2021-07-03T09:19:48Z
• Authors: Matthew D Folchert; Nicole K Littlejohn; Xuebo Liu; Justin L Grobe; Curt D Sigmund
• Keywords: Knockout mouse; Cre recombinase; Northern blot

Renin gene expression is regulated by two distinct promoter-first exon combinations that target renin for either secretion (exon 1a initiating secreted renin, sREN) or cytoplasmic retention 1b intracellular icREN). The icREN isoform expressed predominantly in the brain and its downregulated whereas sREN upregulated deoxycorticosterone (DOCA)-salt suggesting each may be differentially regulated. We generated mice conditionally lack icREN, but preserve sREN, targeting a novel allele ES cells flanking exon-1b surrounding sequences (including promoter) with loxP sites. Mice carrying this were first bred flippase to remove neo cassette then cre-recombinase generate null lacking icREN. structure of final was confirmed Southern blot. There no apparent lethality homozygous when heterozygous intercrossed. Real time quantitative RT-PCR analysis revealed loss mRNA brain, preservation kidney. Male icREN-KO similar size (n=4, 14.7±0.9 wk, 27.94±1.08 g) compared littermate controls (n=7, 14.2±0.8 27.96±0.82 g, P=0.988), NMR exhibited reduced total relative fat mass (1.83±0.15 vs 3.00±0.12 6.6±0.7 10.9±0.5 %, both P<0.001). Interestingly, interscapular brown adipose (289±77, n=5 68±61 mg, n=9 P=0.04) heart (162±12 129±9 masses increased mice, possibly resting metabolic rate (RMR) blood pressure. Liver kidney normal. Food intake normal (3.25±0.28, n=4 3.14±0.14, n=8 P=0.7), preliminary tests uncovered trends toward RMR (7.67±0.75, 6.93±0.59 g/day, kcal/kg lean/hr, P=0.47) glucose tolerance (2g/kg, 25768±3994, n=3 33734±2854 mg/dL*min, n=8, P=0.157). Studies are ongoing assess arterial Together these data suggest contributes cardiovascular control. Future studies using conditional (icREN-flox) will provide an opportunity dissect neural circuits involved responses.