Cloning of mouse islet amyloid polypeptide gene and characterization of its promoter

Islet amyloid polypeptide (IAPP) was isolated from islet amyloid deposits in patients with insulinoma and pancreatic islets of non-insulin-dependent diabetes mellitus (NIDDM) and several reports suggested that it may contribute to the development of NIDDM. IAPP is mainly expressed and synthesized in pancreatic B cells and cosecreted with insulin, so analysis of the transcriptional regulation of the IAPP gene would be helpful for the elucidation of pancreatic B cell specific gene expression. The mouse IAPP gene spans about 5.8 kb and, like the human and rat genes, it consists of three exons, and analysis of the promoter/enhancer activity of mouse IAPP gene reveals the region from -171 to -87 bp to be essential. Within this region, an E-box like sequence, CACCTG (-122 to -117 bp), and a TAAT-box like sequence, TTAATG (-139 to -134 bp), are thought to be important. The disruption of each sequence resulted in a severe decrease in promoter activity, although the decrease was less in the disruption of the E-box than that of TAAT-box like sequence, suggesting the latter is more important for IAPP gene transcription. Like the rat IAPP gene, the CCAAT-box, which does not exist in the human gene, was identified in the mouse gene, indicating the possibility of species difference in the IAPP gene transcriptional mechanism. An enhancer-like activity was also identified within intron 1, although further elucidation is necessary.