CONTROL OF IRBP GENE EXPRESSION IN THE EYE

Henry M. Jackson Fdn For The Adv Mil/Med, Rockville MD

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Abstract

DESCRIPTION (Adapted from applicant's abstract): The long term goal of this project is to define the specific DNA elements required for the control of the spatial and temporal expression of the IRBP gene. Initial experiments will study the DNA elements located within two specific regions of the IRBP gene and its 5'-flanking region and will define the DNA sequences necessary for pan-retinal and tissue-specific expression of the IRBP gene. The experimental approach is to construct and analyze IRBP/reporter gene expression in transgenic mice. The research is based upon two hypotheses: (1) that there is a conserved upstream region (IRBP-CUE) that controls the topographical expression of IRBP and is mandatory for pan-retinal IRBP expression; and (2) that there is a proximal repressor element (IRBP-PRE) within exon 1 that inhibits IRBP expression in all cells except the retinal photoreceptor cells and the pinealocytes by binding a ubiquitous protein, a retina-specific protein can inactivate this complex. The specific aims are: (1) to define the DNA sequences in the IRBP-CUE that control the topographic expression of IRBP in the retina; and (2) to define the DNA sequences in the IRBP first exon that repress IRBP expression in most tissues. The results will define DNA sequences that control IRBP expression and could lead to the identification of IRBP gene fragments useful in targeting reagents to the retina.