title: Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration.
abstract: The NRL gene encodes an evolutionarily conserved basic motif-leucine zipper transcription factor that is implicated in regulating the expression of the photoreceptor-specific gene rhodopsin. NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult. To understand regulation of NRL expression and to investigate its possible involvement in retinopathies, we have determined the complete sequence of the human NRL gene, identified a polymorphic (CA)n repeat (identical to D14S64) within the NRL-containing cosmid, and refined its location by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa (arRP) has been linked to markers at 14q11 and since mutations in rhodopsin can lead to RP, we sequenced genomic PCR products of the NRL gene and of the rhodopsin-Nrl response element from a panel of patients representing independent families with inherited retinal degeneration. The analysis did not reveal any causative mutations in this group of patients. These investigations provide the basis for delineating the DNA sequence elements that regulate NRL expression in distinct neuronal cell types and should assist in the analysis of NRL as a candidate gene for inherited diseases/syndromes affecting visual function.
authors.affiliation: Department of Ophthalmology, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Farjo
authors.forename: A
authors.initials: A
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Pieke-Dahl
authors.forename: K
authors.initials: K
authors.lastname: Scott
authors.forename: W J
authors.initials: WJ
authors.lastname: Kimberling
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
authors.forename: J E
authors.initials: JE
authors.lastname: Richards
authors.forename: A
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018900:Dinucleotide Repeats; D005136:Eye Proteins / Q000235:genetics*; D051790:G-Box Binding Factors; D008040:Genetic Linkage; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D051790:G-Box Binding Factors; C490037:NRL protein, human; C084884:Nrl protein, mouse; D014157:Transcription Factors; D004247:DNA