The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation

We have recently reported that human keratinocytes express both the full-le ngth calcium sensing receptor (CaR) and an alternatively spliced form lacki ng exon 5, which were suggested to be involved in calcium induced keratinoc yte differentiation. To understand further the role of these CaRs, we analy zed the structure of mouse CaRs, and investigated their role using a mouse model in which only the full-length CaR was disrupted. Our results show tha t both the full-length and the alternatively spliced variant lacking exon 5 encoding 77 amino acids of the extracellular domain were expressed in mous e epidermis. The deletion of the full-length CaR increased the production o f the alternatively spliced form of CaR in mutant mice. The keratinocytes d erived from these mutant mice did not respond to extracellular calcium, sug gesting that the full-length CaR is required to mediate calcium signaling i n the keratinocytes. The loss of the full-length CaR altered the morphologi c appearance of the epidermis and resulted in a reduction of the mRNA and p rotein levels of the keratinocyte differentiation marker, loricrin. These r esults indicate that CaR is important in epidermal differentiation, and tha t the alternatively spliced form does not fully compensate for loss of the full-length CaR.