Disease relevance of NR2E3

• Mutations in the human NR2E3 gene and its mouse ortholog are associated with enhanced S-cones and retinal degeneration [1].
• CONCLUSIONS: We found that ESCS, GFS, and CPRD can all have the same genetic basis.Clinical Relevance The combination of night blindness, hyperopia, and clumped retinal pigment deposits should raise the suspicion that a patient has NR2E3 disease [2].
• In human cell lines, PNR expression was observed in Y79 retinoblastoma along with other photoreceptor marker genes such as CRX [3].
• Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice [4].
• The retinal degeneration 7 (rd7) mouse is a naturally occurring model of enhanced S-cone syndrome, Goldman-Favre syndrome and clumped pigmentary retinopathy in humans, allelic disorders caused by inactivation of a photoreceptor-specific nuclear hormone receptor, NR2E3 [5].

Psychiatry related information on NR2E3

• A joint factor analysis of the ESCS and the NEO Personality Inventory (NEO-PI) scales led to a 5-factor solution, where all the factors that emerged were identified as the Big Five personality dimensions, the ESCS subscales loading most significantly on 3 of these factors: Neuroticism (N), Extraversion (E), and Openness to Experience (O) [6].

High impact information on NR2E3

• Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis [7].
• In 16 ESCS patients with the most common NR2E3 mutation, R311Q, we documented an abnormal ratio of S to L/M cone function and progressive retinal degeneration [8].
• Together with the orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct from, but related to the classical biogenic amine receptors [9].
• In situ hybridization with multiple probes on both primate and mouse eye sections demonstrates that RNR is expressed in the retinal pigment epithelium and in Müller glial cells [10].
• The important role of the RNR in DNA synthesis and cell division makes this enzyme an excellent target for chemotherapy [11].

Chemical compound and disease context of NR2E3

• The interaction of the beta-d and beta-l stereoisomers of 2'-azido-2'-deoxyuridine 5'-diphosphate with purified Escherichia coli RNR was also examined [12].

Biological context of NR2E3

• The yeast two-hybrid screening of a retinal cDNA library, using NR2E3 as the bait, identified another orphan nuclear receptor NR1D1 (Rev-erbalpha) [1].
• Assignment of the NR2E3 gene to mouse chromosome 9 and to human chromosome 15q22.33-->q23 [13].
• No mutations were found in the coding exons and splicing junctions of NR2E3, SMAD6, and CLN6 [14].
• In contrast, transcripts for genes associated with phototransduction (RHO), photoreceptor development (NR2E3), or interphotoreceptor matrix constituents (IMPG1) were nearly absent from the GCL fraction [15].
• Hematoxylin/eosin staining of rd7 tissue shows that the whorls in the outer nuclear layer of the retina do not appear during embryonic development but manifest by postnatal day 12.5 (P12.5) [4].

Anatomical context of NR2E3

• NR2E3, a photoreceptor-specific orphan nuclear receptor, is believed to play a pivotal role in the differentiation of photoreceptors [1].
• The subject (Patient A) with no detected NR2E3 mutation had features not usually associated with ESCS, in particular moderate rod photoreceptor function in peripheral retina and an abnormally thick retinal nerve fibre layer [16].
• Our studies suggest that, based on its temporal and spatial expression, NR2E3 acts simultaneously in different cell types: in late mitotic progenitors, newly differentiating post mitotic cells, and mature rods and cones [17].
• NR2E3 mRNA was detected in the adrenal gland, thyroid gland, prostate, testis, uterus, trachea, and salivary gland [18].
• It examines the relationship between the effectiveness of epidural spinal cord stimulation (ESCS) and diseases or sites of pain [19].

Associations of NR2E3 with chemical compounds

• The interaction of NR2E3 with NR1D1 was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation experiments [1].
• The frequency of triplets decays in the order RNY greater than RNR greater than YNY greater than YNR; R being a purine (guanine or adenine), Y is a pyrimidine (cytosine or uracil), and N is any base [20].
• An oligodeoxynucleotide phosphorothioate that is complementary to sequences around the translational initiation codon of the small RNR subunit showed significant inhibition of growth, as measured by the inhibition in DNA synthesis [11].
• In this report, we examined the mode of nitrite reductase (PNR) release from a serum-sensitive strain of live P. aeruginosa cells during in vitro treatment with four different antimicrobial agents or human complement [21].
• Among these agents, imipenem demonstrated rapid killing of P. aeruginosa as well as rapid release of PNR and resulted in the highest IL-8 production [21].

Other interactions of NR2E3

• RESULTS: NR2E3 expression was detected shortly after the appearance of NRL in putative immature rods on the foveal edge at Fwk 11 [22].
• Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes but an activator of only a subset of rod genes (including rhodopsin) in vivo [23].
• NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation [23].
• The CPRD patients without NR2E3 mutations had no detected mutations in NRL or THRB1 [2].
• Mutation screening of the NR2E3 gene, which encodes a photoreceptor-specific orphan nuclear receptor, was performed with polymerase chain reaction amplification and direct sequencing [24].

Analytical, diagnostic and therapeutic context of NR2E3

• In order to gain insights into the NR2E3 function, we performed temporal and spatial expression analysis, yeast two-hybrid screening, promoter activity assays and co-immunoprecipitation studies [1].
• METHODS: Expression of NR2E3, a photoreceptor-specific orphan nuclear receptor, was examined in human retinas between fetal weeks (Fwk) 9 to 22 by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization [22].
• Both NR2E3 and NRL expression patterns were followed by immunocytochemistry [22].
• Northern blot and reverse transcription-PCR analyses of human mRNA samples demonstrate that RNR is expressed exclusively in the retina, with transcripts of approximately 7.5 kb, approximately 3.0 kb, and approximately 2.3 kb by Northern blot analysis [10].
• Mutation screening of the NR2E3 gene was performed with polymerase chain reaction (PCR) amplification and direct sequencing [25].

References