title: Cloning of mouse islet amyloid polypeptide gene and characterization of its promoter.
abstract: 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.
authors.affiliation: First Department of Medicine, Wakayama University of Medical Science, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ekawa
authors.forename: M
authors.initials: M
authors.lastname: Nishi
authors.forename: S
authors.initials: S
authors.lastname: Ohagi
authors.forename: T
authors.initials: T
authors.lastname: Sanke
authors.forename: K
authors.initials: K
authors.lastname: Nanjo
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D006801:Humans; D058228:Islet Amyloid Polypeptide; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D015500:Chloramphenicol O-Acetyltransferase