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J. Biol. Chem. 275 (2): 1183-1190

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

J Biol Chem, Vol. 275, Issue 2, 1183-1190, January 14, 2000

The Calcium Sensing Receptor and Its Alternatively Spliced Form in Murine Epidermal Differentiation*

Yuko OdaDagger §, Chia-Ling Tu, Wenhan Chang, Debra CrumrineDagger , László KömüvesDagger , Theodora MauroDagger , Peter M. EliasDagger , and Daniel D. Bikle

From the Departments of Dagger  Medicine and Dermatology and  Endocrinology, University of California San Francisco, Veterans Affairs Medical Center, San Francisco, California 94121

We have recently reported that human keratinocytes express both the full-length calcium sensing receptor (CaR) and an alternatively spliced form lacking exon 5, which were suggested to be involved in calcium induced keratinocyte differentiation. To understand further the role of these CaRs, we analyzed 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 that both the full-length and the alternatively spliced variant lacking exon 5 encoding 77 amino acids of the extracellular domain were expressed in mouse epidermis. The deletion of the full-length CaR increased the production of the alternatively spliced form of CaR in mutant mice. The keratinocytes derived from these mutant mice did not respond to extracellular calcium, suggesting that the full-length CaR is required to mediate calcium signaling in the keratinocytes. The loss of the full-length CaR altered the morphologic appearance of the epidermis and resulted in a reduction of the mRNA and protein levels of the keratinocyte differentiation marker, loricrin. These results indicate that CaR is important in epidermal differentiation, and that the alternatively spliced form does not fully compensate for loss of the full-length CaR.

* This work was supported by Grants R01-AR38386 and P01-AR39448 from the National Institutes of Health and by a Merit Review award from the Department of Veterans Affairs.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF110178 and AF110179.

§ To whom correspondence should be addressed: Endocrine 111N, Veterans Affairs Medical Center, 4150 Clement St., San Francisco, CA 94121. Tel.: 415-221-4810 (ext. 3331); Fax: 415-750-6929; E-mail: y2073@itsa.ucsf.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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