Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PA
S domain transcription factor expressed in multiple regions of the vertebra
te brain. Targeted insertion of a beta-galactosidase reporter gene (lacZ) r
esulted in the production of an NPAS2-LacZ fusion protein and an altered fo
rm of NPAS2 Lacking the bHLH domain. The neuroanatomical expression pattern
of NPAS2-lacZ was temporally and spatially coincident with formation of th
e mature frontal association/limbic forebrain pathway. NPAS2-deficient mice
were subjected to a series of behavioral tests and were found to exhibit d
eficits in the Long-term memory arm of the cued and contextual fear task. T
hus, NPAS2 may serve a dedicated regulatory role in the acquisition of spec
ific types of memory.