HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Buy All Versions of this Article: fj.08-117739v1 23/6/1766    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kalea, A. Z. Articles by Hudson, B. I. Search for Related Content PubMed PubMed Citation Articles by Kalea, A. Z. Articles by Hudson, B. I.

Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene

^* Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York, USA

¹Correspondence: Division of Surgical Science, Dept. of Surgery, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., P&S 17-401, New York, NY 10032, USA. E-mail: bh2021{at}columbia.edu

The alternative splicing of pre-mRNAs is a critical mechanism in genomic complexity, disease, and development. Studies of the receptor for advanced glycation end-products (RAGE) indicate that this gene undergoes a variety of splice events in humans. However, no studies have extensively analyzed the tissue distribution in other species or compared evolutionary differences of RAGE isoforms. Because the majority of studies probing RAGE function have been performed in murine models, we therefore performed studies to identify and characterize the splice variants of the murine RAGE gene, and we compared these to human isoforms. Here, using mouse tissues, we identified numerous splice variants including changes in the extracellular domain or the removal of the transmembrane and cytoplasmic domains, which produce soluble splice isoforms. Comparison of splice variants between humans and mice revealed homologous regions in the RAGE gene that undergo splicing as well as key species-specific mechanisms of splicing. Further analysis of tissue splice variant distribution in mice revealed major differences between lung, kidney, heart, and brain. To probe the potential impact of disease-like pathological states, we studied diabetic mice and report that RAGE splice variation changed dramatically, resulting in an increase in production of soluble RAGE (sRAGE) splice variants, which were not associated with detectable levels of sRAGE in murine plasma. In conclusion, we have determined that the murine RAGE gene undergoes extensive splicing with distinct splice isoforms being uniquely distributed in different tissues. These differences in RAGE splicing in both physiological and pathogenic states further expand our understanding of the biological repertoire of this receptor in health and disease.—Kalea, A. Z., Reiniger, N., Yang, H., Arriero, M., Schmidt, A. M., Hudson, B. I. Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene.

Key Words: DNA cloning • mRNA • soluble receptor • species-specific splicing • protein evolution