Disease relevance of Rbp3

• Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact [1].
• We demonstrate that MOK2 can bind to the 8-bp sequence present in the IRBP promoter and repress its transcription when transiently overexpressed in retinoblastoma Weri-RB1 cells [2].
• Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU) [3].
• Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors [4].
• Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle [4].

High impact information on Rbp3

• Susceptibility to experimental autoimmune uveitis (EAU), a model for human uveitis induced in mice with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP), is controlled by "natural" CD4(+)CD25(+) regulatory T (T reg) cells [5].
• Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity [5].
• In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity [6].
• The KO mice had greatly elevated responses to IRBP, an altered recognition of IRBP epitopes, and their primed T cells induced exacerbated disease in WT recipients [7].
• IRBP is believed to serve as a carrier for retinoids in the bleaching and regeneration cycle of rhodopsin [8].

Chemical compound and disease context of Rbp3

• Rhodopsin regeneration requires attachment between the retinal pigment epithelium (RPE) and rod outer segments; however, in experimentally induced retinal detachment, rhodopsin regeneration can be restored partially upon addition of IRBP (interphotoreceptor retinoid binding protein) [9].
• The minimal effective protocol for EAU induction when the vaccine form of B. pertussis adjuvant was used consisted of pretreatment with cyclophosphamide, two divided doses of IRBP in complete Freund's adjuvant (CFA), and two divided doses of B. pertussis vaccine [10].
• The pathogenicity of interphotoreceptor retinoid-binding protein (IRBP) in the mouse and H-2 restriction of IRBP-induced experimental autoimmune uveoretinitis (EAU) was tested by repeated immunization using Klebsiella pneumoniae 03 lipopolysaccharide (K03-LPS) as an adjuvant [11].

Biological context of Rbp3

• Bmpr is closely linked to Rbp3 in the region containing pugnose, a mutation that alters bone development [12].
• Timing of interphotoreceptor retinoid-binding protein (IRBP) gene expression and hypomethylation in developing mouse retina [13].
• Taken together, these results indicate that IRBP gene activation is associated with hypomethylation during the last mitosis before photoreceptor cell differentiation [13].
• We have used a 900-bp bovine IRBP cDNA fragment to map the corresponding gene, Rbp-3, to mouse chromosome 14 with somatic cell hybrids and have positioned the gene near Np-1 (nucleoside phosphorylase-1) by analysis of the progeny of an intersubspecific backcross [14].
• Interphotoreceptor retinoid binding protein (IRBP) is a retinoid and fatty acid binding glycoprotein secreted by rod and cone photoreceptors in all vertebrates [8].

Anatomical context of Rbp3

• A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene [1].
• These findings support the hypothesis that IRBP is synthesized by the rods and cones, and suggest that its synthesis and secretion are initiated when the photoreceptor inner segments start to differentiate [15].
• Interphotoreceptor retinoid-binding protein (IRBP) is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium and the photoreceptor cells [14].
• DNA/protein binding assays, performed to identify binding sites for tissue-specific trans-acting factors, have shown that an element between -45 and -58 binds a factor present only in nuclear extracts of retinoblastoma-derived cell lines, which express IRBP [16].
• Ambient light appears to play a role in regulating gene and protein expression of interphotoreceptor retinoid-binding protein (IRBP), a protein that facilitates the transport of retinoids between the neural retina and pigment epithelium in the visual cycle [17].

Associations of Rbp3 with chemical compounds

• We determined during photoreceptor development if there is a retina-specific hypomethylation of the mouse gene encoding interphotoreceptor retinoid-binding protein (IRBP) that is associated with its activation [13].
• Cells positive for both IRBP and BrdU were always observed as soon as 2 hr after injection but it took at least 40 hr before they became positive for both opsin and BrdU [13].
• These results suggest that the regulation of IRBP by retinol is not transcriptional [8].
• To understand the mechanism for this recovery, we determined whether vitamin A affects transcription and translation of the IRBP gene [8].
• Wild-type and transgenic mice harboring the IRBP promoter-CAT reporter fusion gene were maintained on a retinol-deficient diet supplemented with retinoic acid (-A) or on a control diet (+A) for up to 60 wk postweaning [8].

Regulatory relationships of Rbp3

• Synthesis and secretion of IRBP in vitro was less than 10% of the controls in rd retinas at P26, when only 4-5% of the photoreceptors survived [15].

Other interactions of Rbp3

• Rhodopsin and IRBP increased in parallel with ROS elongation up to P25, when the ROS had reached their mature lengths [15].
• Second, the role of IRBP gene and protein expression in development was assessed by determining if their expression occurs before that of opsin [13].
• Furthermore, we show that Mok2 expression in the developing mouse and in the adult retina seems to be concordant with IRBP expression [2].
• Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin) [4].
• IRBP and RAG1 molecular clocks for Mus date the origin of subgenera to around 5-6 mya and the origin of Species Groups within subgenus Mus to around 2-3 mya [18].

Analytical, diagnostic and therapeutic context of Rbp3

• IRBP message was PCR amplified from these cells after microdissection [7].
• Northern blots showed no differences in the amounts of IRBP or CAT mRNA between these three treatment groups [8].
• Immunocytochemical and Western blot analyses demonstrated the absence of IRBP expression in the IRBP-/- mice [19].
• Light microscopic examination of the light-deprived mouse retinas showed no apparent abnormalities in morphological development and immunocytochemistry demonstrated normal distribution and levels of IRBP protein [17].
• METHODS: We examined the distribution of albumin in IRBP-/- mice and IRBP+/+ mice using immunofluorescence and immunoperoxidase histochemistry [20].

References