Differential Expression of Murine Renal Genes in Olfactory Receptor 78 Null Mice

Abstract

The microbiome has been implicated in blood pressure regulation and recent studies have found that gut‐derived microbial short chain fatty acids (SCFAs) modulate blood pressure. This is mediated, at least in part, by Olfactory receptor 78 (Olfr78), a G‐protein coupled receptor (GPCR) which responds to SCFAs to modulate renin release. Other renal GPCRs which respond to SCFAs include Olfr558, Gpr41, and Gpr43. Although we have previously studied the physiology of Olfr78 null mice, we do not know whether the expression of the other SCFA receptors, or other key renal genes, are altered in these animals. To address this, we extracted RNA from murine kidneys (8 Olfr78 WTs and 5 Olfr78 KOs) and performed reverse transcription and quantitative PCR using Taqman probe sets for 2 SCFA ORs (Olfr78, Olfr558), 2 SCFA GPCRs (Gpr41, Gpr43), as well as genes of interest (Renin1, Avpr2, Aqp2, ENaC, ROMK, BKA, and Wnt5a), and Gapdh as a control. From our screen, three genes were significantly decreased (p<0.05) in Olfr78 null mice when compared to WT: Olfr558 (mean fold change ± s.d., WT 1 ± 0.49, KO 0.34 ± 0.26), Aqp2 (WT 1 ± 0.51, KO 0.25 ± 0.11), and ROMK (WT 1 ± 0.36, KO 0.52 ± 0.20). The other genes assayed did not change between genotypes. Although we are not properly powered to examine sex, we did include both males and females and did not note any sex differences. Notably, novel changes in Aqp2 and ROMK expression imply potential changes in water or potassium handling in these animals. Future studies will include RNAScope and immunohistochemistry confirmation of these findings, as well as functional studies to determine the consequences of these changes.