MOLECULAR-CLONING OF MOUSE PANCREATIC-ISLET R-CADHERIN - DIFFERENTIALEXPRESSION IN ENDOCRINE AND EXOCRINE TISSUE

A search for novel pancreatic islet cadherins was undertaken using the polymerase chain reaction with mouse betaTC3 cell line cDNA and degen erate primers based on conserved C-terminal sequence in neural (N), ep ithelial, and placental cadherin (CAD). A hitherto uncharacterized rod ent sequence was detected which was then cloned from a mouse insulinom a cDNA library and shown to be the mouse equivalent of chicken retina CAD (R-CAD). The similarity of the mouse and chicken sequences was rem arkable (eight nonconservative changes in the 747 amino acids of the m ature protein sequence; 95% overall identity), indicating strong conse rvation of function. Mouse R-CAD was also closely homologous to N-CAD (72% identity), including those regions of N-CAD implicated in the cad herin-cadherin interaction and Ca2+ binding. In vitro translation of t he cDNA indicated that mouse R-CAD enters the secretory pathway and un dergoes posttranslational glycosylation and proteolytic cleavage. R-CA D mRNA was distributed widely in mouse tissues with high levels presen t in brain, skeletal muscle, and thymus. In the pancreas, R-CAD and N- CAD showed endocrine cell specificity and a differential expression in beta- and non-beta-cells. Messenger RNA expression was evident during early pancreatic development at a time when the first pluripotent hor mone-producing cells differentiate to attain their adult phenotype and become organized in islet-like clusters. The presence of R-CAD and N- CAD in islets is consistent with the neurone-like properties of this t issue. Differences in CAD expression might explain the segregation of exocrine and endocrine cells during development of the pancreas and th e characteristic morphological distribution of the different endocrine cells within the islet.