TRANSGENIC AND TRANSCRIPTIONAL STUDIES ON NEUROSECRETORY CELL GENE-EXPRESSION

1. Studies of the regulation of neurosecretory cell gene expression su ffer from the lack of suitable cell lines. Two approaches have been us ed to overcome this deficit: transfection of neuropeptide genes into h eterologous cell lines and generation of transgenic animals. 2. Studie s with heterologous cell lines have revealed the potential involvement of nuclear hormone receptors, POU proteins, and fos/jun/ATF family me mbers in the regulation of the vasopressin and oxytocin genes. Althoug h limited in their scope, these studies have contributed greatly to th e dissection of basic properties of elements in the vasopressin and ox ytocin gene promoters. 3. Transgenic mice, and more recently rats, hav e been used to elucidate genomic regions governing cell specificity an d physiological regulation of neurosecretory gene expression. The gene s encoding the neuropeptides vasopressin and oxytocin have been used i n many transgenic studies, due to the well-defined expression patterns and physiology of the endogenous neuropeptides. Cell-specific and phy siologically regulated expression of these transgenes has been achieve d, demonstrating the action of putative repressor elements and regulat ion of the expression of one gene by sequences present in the other ge ne. 4. Appropriate expression and translation of transgenes have resul ted in the production of several useful systems. Expression of oncogen e sequences in gonadotropin-releasing hormone neurons has allowed the development oi cell lines from the resulting tumors, overproduction of corticotropin-releasing factor has produced animal models of anxiety and obesity, and directed ectopic expression of growth hormone has gen erated a potentially useful rat model of dwarfism. These and other ani mal models of human disease will provide important avenues for the dev elopment of therapeutic strategies.