CELL-SPECIFIC EXPRESSION OF THE HUMAN GONADOTROPIN-RELEASING-HORMONE GENE IN TRANSGENIC ANIMALS

We have previously demonstrated that 1131 base pairs (bp) of the human gonadotropin-releasing hormone (hGnRN) gene promoter can target simia n virus 40 T antigen expression to GnRH neurons in transgenic mice. In these animals, GnRH neurons were transformed before they migrated to their final location in the rostral hypothalamus, complicating an anal ysis of cell-specific expression. To localize regions of the hGnRB pro moter that are important for cell-specific expression, we created tran sgenic mice with various 5'-flanking regions of the hGnRH gene fused t o the luciferase reporter gene, When 3828 or 1131 bp of the hGnRH prom oter 5'-flanking DNA were used (-3828/+5LUC and -1131/+5LUC, respectiv ely), luciferase expression in adult transgenic mice was observed in t he rostral hypothalamus and olfactory tissues, regions which have been shown to be loci of GnRH-expressing neurons, Luciferase expression wa s not observed in other brain or peripheral tissues. Double-labeled in situ hybridization further demonstrated that luciferase expression wa s invariably colocalized with GnRH expression. When transgenic animals were created with a construct consisting of 484 bp of the hGnRH 5'-fl anking DNA fused to the luciferase gene (-484/+5LUC), luciferase expre ssion was not observed in the hypothalamus or in olfactory tissues. Th is is the first report localizing DNA sequences responsible for cell-s pecific expression of the GnRH gene in vivo.