CALCIUM SENSING RECEPTOR DELETION IN THE MOUSE ESOPHAGUS ALTERS THE EXPRESSION OF CELL‐CELL JUNCTIONAL PROTEINS

Abstract

Calcium sensing receptor (CaSR) is the molecular sensor by which cells respond to small changes in extracellular Ca+2 concentration. It regulates Ca+2 homeostasis by modulating PTH secretion and Ca+2 reabsorption in the kidney. CaSR also plays a role in glandular and fluid secretion in the GI tract and regulates differentiation and proliferation of keratinocytes. CaSR is present in the esophageal epithelium, but its role in this tissue has not been defined. We deleted CaSR in the mouse esophagus by generating KRT5‐CreER;CaSRloxP/loxP compound mutants, where loxP sites flank exon 7 of CaSR gene. For lineage tracing of epithelial cells we bred‐in the reporter allele Rosa26R. Recombination was initiated with multiple tamoxifen injections. We demonstrated exon 7 deletion and Cre expression by PCR analysis of genomic DNA and LacZ staining. qRT‐PCR & Western blot (WB) analyses showed a significant reduction in CaSR mRNA & protein expression as compared to control CaSRloxP/loxP mice. Microscopic examination of esophageal tissues (H&E) did not show gross abnormalities. However, WB data revealed a significant reduction (~25%) in levels of adherens junction proteins E‐cadherin and β catenin and tight junction protein claudin‐1. Levels of Rac/Cdc42, small GTPase proteins involved in actin remodeling, were also reduced. Our data indicate that CaSR plays a role in regulating cell‐cell junctional complexes and is therefore important for the maintenance of the barrier properties in the esophagus.Support: VA Merit & Tulane Enhancement Award