Genomic organization and chromosomal localization of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene: a candidate for 6q-linked retinopathies

Abstract

The interphotoreceptor matrix is a unique extracellular matrix occupying the space between the photoreceptors and the retinal pigment epithelium. Due to its putative function in the maintenance and integrity of the photoreceptor cells, it is conceivable that it is involved in retinal degeneration processes. More recently, a novel gene encoding a 150-kDa interphotoreceptor matrix proteoglycan, designated IMPG1, was cloned and shown to be expressed in both rod and cone photoreceptor cells. To assess this gene in human retinal dystrophies, we have now determined the genomic organization and chro- mosome location of IMPG1. It is composed of 17 exons ranging from 21 to 533 bp, including an alternatively spliced exon 2. Using somatic cell hybrid mapping and FISH analysis, we have assigned the IMPG1 locus to 6q13→q15. As this interval overlaps with the chromosomal loci of several human retinopathies, including autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1), IMPG1 represents an attractive candidate for these 6q-linked disorders.

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

“…The deposit is estimated to be approximately 50 μm, containing a mixture of substances rich in lipids, collagen mucopolysaccharide, elastin, Muller cell processes and rhodopsin-positive neurons extending from the central retina to the ora serrata (Kuntz et al, 1996;Milam et al, 4.1.6 IMPG1 and IMPG2 carriers IMPG1 (interphotoreceptor matrix proteoglycan 1) encodes SPACR, a 150kDa sialoprotein associated with rod and cone photoreceptors. It is a major component of the interphotoreceptor matrix, the site where rods and cones interact with the RPE (Felbor et al, 1998;Kuehn and Hageman, 1999). SPACR is highly homologous to SPACRCAN (sialoprotein associated with photoreceptor cone and rod proteoglycans), a 200 kDa protein encoded by IMPG2 (interphotoreceptor matrix proteoglycan 2) and also found in the interphotoreceptor matrix (Acharya et al, 2000).…”

Mucin-Like Glycoprotein Associated with Photoreceptor Cells in the Postnatal Developing Rat Retina

“…The predicted sequence also contains two hyaluronan-binding consensus sequences [18] in the N-terminal domain together with a number of serine and threonine residues in the center domain. These characteristic domains are preserved in the human [5][6][7], bovine [8] and rat core proteins and may be involved in the organization of the retina including extracellular adhesion.…”

“…It showed 61.5% identity with that of the bovine MLGAPC core protein (AB047843) [8]. A search of the GenBank revealed that the predicted amino acid sequence of the rat MLGAPC core protein showed 64.4% nucleotide similarity with that encoded by the human cDNA of IMPG1 [5,7] (AF017776). The predicted molecular size of the protein (798 amino acids) was 89,852 D. In the predicted amino acid sequence, a signal anchor sequence, Ala8-Leu16, was detected.…”

“…Retinoids are transported between photoreceptors and the retinal pigment epithelium (RPE), which is mediated by the interphotoreceptor retinoid-binding protein (IRBP) in the IPM [2][3][4]. In addition to this soluble component, several glycoproteins with O-linked sugar chains, IPM proteoglycan-1 (IMPG1) [5,6] and sialoprotein associated with cones and rods (SPACR) [7] have been isolated from the human IPM and considered to be involved in the organization and maintenance of its insoluble structure [5][6][7].…”

“…The cDNA encodes the entire core protein for JBGP with a relative mass of 120 kD (asialo-type) and 135 kD (sialo-type) [8]. Since the JBGP core protein is distributed not only in the photore- Uehara/Ohba/Ozawa ceptor layer but also in the cone pedicles and rod spherules, we proposed the term 'mucin-like glycoprotein associated with photoreceptor cells (MLGAPC)', which reflects the distribution and features of the protein better than IMPG1 [5,6], SPACR [7], or JBGP [8].…”