Specific gene expression in pancreatic beta-cells - Cloning and characterization of differentially expressed genes

Identification and characterization of genes expressed preferentially in pa ncreatic beta-cells will clarify the mechanisms involved in the specialized properties of these cells, as well as providing new markers of the develop ment of type I diabetes. Despite major efforts, relatively fen beta-cell-sp ecific genes have been characterized. We applied representational differenc e analysis to identify genes expressed selectively in the pancreatic beta-c ell line beta TC1 compared with the pancreatic alpha-cell line alpha TC1 an d isolated 26 clones expressed at higher levels in the beta-cells than in t he alpha-cells, DNA sequencing revealed that 14 corresponded to known genes (that is, present in GenBank), Only four of those genes had been shown pre viously to be expressed at higher levels in beta-cells (insulin, islet amyl oid polypeptide, neuronatin, and protein kinase A regulatory subunit [RI al pha]). The known genes include transcription factors (STAT6) and mediators of signal transduction (guanylate cyclase). The remaining 12 genes are abse nt from the GenBank database or are present as expressed sequence tag (EST) sequences (4 clones). Some of the genes are expressed in a highly specific pattern-expression in beta TC1 and islet cells and in relatively few of th e non-beta-cell types examined; others are expressed in most cell types tes ted. The identification of these differentially expressed genes may aid in attaining a dearer understanding of the mechanisms involved in beta-cell fu nction and of the possible immunogens involved in development of type 1 dia betes.