THE MURINE Y-1 RECEPTOR 5' UPSTREAM SEQUENCE DIRECTS CELL-SPECIFIC AND DEVELOPMENTALLY-REGULATED LACZ EXPRESSION IN TRANSGENIC MICE CNS

The Y-1 receptor for neuropeptide Y (NPY) is highly expressed in mamma lian CNS where it mediates the activation of several neurobiological f unctions. We have previously demonstrated that a 1,3-kb fragment upstr eam of the transcription initiation sites of the murine Y1 receptor ge ne is able to direct specific expression of reporter genes in neuronal cell cultures. In the present study transgenic mice harbouring this p utative promoter region linked to the LacZ reporter gene were generate d and analysed for temporal and spatial distribution. Ten transgenic l ines expressed beta-galactosidase in the CNS but not in other organs s uch as heart, liver and kidney. Histochemical analysis of brain from a dult transgenic mice showed specific expression of the transgene in sp ecific brain regions with little variation. Four transgenic lines show ed characteristic patterns of beta-galactosidase activity in the brain that are consistent with the expression of the endogenous gene. Promi nent LacZ activity was present in several telencephalic and diencephal ic structures, including deeper layers of cerebral cortex, amygdaloid complex, hippocampus, preoptic area, several thalamic and hypothalamic nuclei and habenula. The ontogeny analysis indicates that the LacZ ex pression agrees with the temporal expression pattern of rat Y-1 recept or mRNA. These data demonstrate that the 1.3-kb upstream region of the murine Y-1 receptor gene contains the cis acting elements required fo r establishing a CNS-restricted and developmental stage-specific patte rn of expression in vivo. Moreover they provide further information on the distribution of this NPY subtype receptor in mammalian brain.