title: Effects of mutation of the Olf-1 motif on transgene expression in olfactory receptor neurons.
abstract: We have examined the effect of mutating the Olf-1 binding motif of the olfactory marker protein (OMP) promoter in determining olfactory neuron-specific gene expression in adult tissues and during embryonic development. The proximal Olf-1 motif located 170 nucleotides upstream of the transcription start site of the OMP gene was mutated to prevent its interaction with the Olf-1 factor in vitro. The wild-type and mutated fragments of the OMP gene extending from -239 to +55 nucleotides relative to the transcription start site were used to direct expression of a lacZ reporter gene in transgenic mice. The transgenic animals were analyzed for cell-specific and developmental expression of the reporter gene. We demonstrate that the mutation that prevents interaction of Olf-1 with its binding site does not alter the temporal and spatial patterns 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 mutated Olf-1 site interacts with nuclear proteins present in the central nervous system (CNS).
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Kudrycki
authors.forename: O
authors.initials: O
authors.lastname: Buiakova
authors.forename: G
authors.initials: G
authors.lastname: Tarozzo
authors.forename: M
authors.initials: M
authors.lastname: Grillo
authors.forename: E
authors.initials: E
authors.lastname: Walters
authors.forename: F L
authors.initials: FL
authors.lastname: Margolis
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000235:genetics; D051842:Olfactory Marker Protein; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D019076:Transgenes; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; C489920:Ebf1 protein, rat; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; C497599:Omp protein, rat; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D001616:beta-Galactosidase