A comparative kidney transcriptome analysis of bicarbonate-loaded insrr-null mice

The maintenance of physiological pH level is critical for the life of all organisms. Well known, that kidney is key organ for acid-base regulation in vertebrates. Metabolic alkalosis is the most common acid-base disorder in hospitalized patients, particularly in the surgical critical care unit. The receptor tyrosine kinase IRR (insulin receptor-related receptor), a receptor like the insulin receptor, is involved in acid-base regulation by kidney due to its ability to autophosphorylate under alkalization of extracellular medium (pH > 7.9). IRR expressed in only ß-intercalated cells. In mice with a knockout of the insrr gene, which encoding IRR, bicarbonate secretion to the urine is impaired. Here for the first time, we present analysis of kidney transcriptomes from wild type and insrr gene knockout mice under basal or bicarbonate-loaded conditions by 250 mM NaHCO3 in drinking water. Analysis of NGS sequencing data revealed changes in the expression of a number of genes in the kidney. Using real-time PCR we confirmed change of expression of the slc51b, slc26a4, rps7, slc5a2, aqp6, plcd1, gapdh, rny3, lypd2, kcnk5, slc6a6 , atp6v1g3 genes in IRR knockout mice. Also, we found that expression of kcnk5 gene is increased in wild type mice after bicarbonate loading but didn't change in knockout mice. Gene set enrichment between the IRR knockout and wildtype samples identified that knockout causes alterations in expression of genes related mostly to the ATP metabolic and electron transport chain processes. Thus, for the first time, we described some details of the functioning of the IRR in the kidneys. Overall design: Mouse kidney RNA-seq Wild Type and IRR(-/-) mouse with bicarbonate loading and no treatment