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Many genomic, anatomical and functional differences exist between the medullary (MTAL) and the cortical thick ascending limb of the loop of Henle (CTAL), including a higher expression of claudin-10 (CLDN10) in the MTAL than in the CTAL. Therefore, we assessed to what extent the <i>Cldn10</i> gene expression is a determinant of differential gene expression between MTAL and CTAL. RNAs extracted from CTAL and MTAL microdissected from wild type (WT) and Cldn10 knock out mice (cKO) were analyzed by RNAseq. Differential and enrichment analyses (GSEA) were performed with interactive R Shiny software. Between WT and cKO MTAL, 637 genes were differentially expressed, whereas only 76 were differentially expressed between WT and cKO CTAL. Gene expression patterns and GSEA analyses in all replicates showed that WT MTAL did not cluster with the other replicates; no hierarchical clustering could be found between WT CTAL, cKO CTAL and cKO MTAL. Compared to WT replicates, cKO replicates were enriched in <i>Cldn16</i>, <i>Cldn19</i>, <i>Pth1r</i>, (parathyroid hormone receptor type 1), <i>Casr</i> (calcium sensing receptor) and <i>Vdr</i> (Vitamin D Receptor) mRNA in both the cortex and medulla. <i>Cldn10</i> is associated with gene expression patterns, including genes specifically involved in divalent cations reabsorption in the TAL.