ABLATION OF ISLET ENDOCRINE-CELLS BY TARGETED EXPRESSION OF HORMONE-PROMOTER-DRIVEN TOXIGENES

Ontogenic relationships between the different types of endocrine cells in the islets of Langerhans were explored by generating transgenic mo use embryos in which cells transcribing the glucagon, insulin, or panc reatic polypeptide genes were destroyed through the promoter-targeted expression of the diphtheria toxin A chain. Embryos lacking glucagon- or insulin-containing cells did not exhibit alterations in the develop ment of the nontargeted islet cell types, whereas embryos lacking panc reatic polypeptide gene expressing cells also lacked pancreatic insuli n- and somatostatin-containing cells. These results show that neither glucagon nor insulin gene-expressing cells are essential for the diffe rentiation of the other islet endocrine-cell types. These results also suggest that pancreatic polypeptide gene expressing cells are indispe nsable for the differentiation of islet beta and delta cells because t he former produce a necessary paracrine or endocrine factor and/or ope rate through a cell-lineage relationship.