ALTERED GENE STRUCTURE AND TISSUE EXPRESSION OF ISLET AMYLOID POLYPEPTIDE IN THE CHICKEN

In mammals, islet amyloid polypeptide (IAPP) is a putative pancreatic peptide hormone that is coproduced and cosecreted with insulin in the beta-cells. However IAPP is also structurally and functionally similar to calcitonin gene-related peptide (CGRP), a 37-amino acid peptide th at is expressed predominantly in neurones, and it has been suggested t hat these peptides arose from a common ancestral gene. In the present study we have characterized an avian IAPP cDNA and gene and have analy zed their expression in various tissues. The cloned chicken IAPP cDNA encodes a 135-amino acid (aa) precursor in which the mature 37-residue IAPP is 80% identical to human IAPP. However, the N-terminal propepti de of chicken proIAPP (55 aa) is considerably longer than that found i n the mammalian proIAPPs (9-12 aa) and is comparable in length to that of chicken proCGRP (52 aa). Most of this additional peptide material was found to be encoded in an exon of the cloned chicken IAPP gene tha t is homologous to exon 3 in the CORP gene. This exon is absent in the human IAPP gene and thus the exonintron organization of the chicken I APP gene more closely resembles that of mammalian CORP genes. Northern blot analyses demonstrated that chicken IAPP mRNA is expressed predom inantly in intestine and brain but at a much lower level in pancreas. The pancreas and intestine contained a single 0.7 kilobase (kb) IAPP t ranscript while two transcripts, 0.7 kb and 0.9 kb, were detected in b rain. Densitometric analysis indicated that IAPP transcripts were 11 t imes more abundant in brain and intestine than pancreas. Taken togethe r these findings suggest that IAPP functions predominantly as an extra pancreatic neuroendocrine peptide in nonmammalian vertebrates but has evolved to become a pancreatic neuroendocrine peptide in mammals; thus the close coordination of its expression with that of insulin appears to be a more recent feature that first appears in mammals. Whether IA PP has the same physiological functions in mammals and nonmammalian ve rtebrates remains to be determined.