EFFECTS OF MUTATION OF THE OLF-1 MOTIF ON TRANSGENE EXPRESSION IN OLFACTORY RECEPTOR NEURONS

We have examined the effect of mutating the Olf-1 binding motif of the olfactory marker protein (OMP) promoter in determining olfactory neur on-specific gene expression in adult tissues and during embryonic deve lopment. The proximal Olf-1 motif located 170 nucleotides upstream of the transcription start site of the OMP gene was mutated to prevent it s interaction with the Olf-1 factor in vitro. The wild-type and mutate d fragments of the OMP gene extending from -239 to +55 nucleotides rel ative to the transcription start site were used to direct expression o f a lacZ reporter gene in transgenic mice. The transgenic animals were analyzed for cell-specific and developmental expression of the report er gene. We demonstrate that the mutation that prevents interaction of Olf-1 with its binding site does not alter the temporal and spatial p atterns of gene expression in olfactory sensory neurons but does alter the specificity and level of expression in other neuronal populations . These observations are consistent with our demonstration that the mu tated Olf-1 site interacts with nuclear proteins present in the centra l nervous system (CNS). (C) 1998 Wiley-Liss, Inc.