Disease relevance of NR2E1

• Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci [1].
• In fierce mutants carrying human NR2E1, structural brain defects were eliminated and eye abnormalities ameliorated [2].
• The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21 [3].
• It is proposed that such TLX alloantigens are central in establishing maternal recognition and protection of the blastocyst, and that lack of recognition results in implantation failure and spontaneous abortion [4].
• The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group [5].

High impact information on NR2E1

• Antisera to human syncytiotrophoblast microvillous cell surface membranes from different placentas are cytotoxic for lymphocytes from some people but not others, demonstrating the presence of allotypic trophoblast-lymphocyte cross-reactive (TLX) antigens [4].
• Exploratory principal components factor analysis, performed on limited data consisting of 300 cytotoxic reactions produced by ten separate trophoblast antisera on a panel of lymphocytes from 30 random donors, suggested the presence of three distinct TLX antigen groupings [4].
• Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1 [6].
• Ectopic expression of TLX in fibroblasts resulted in increased sensitivity to RA induction, an effect that is conserved between chick and mammals [7].
• We have identified a cis element, the silencing element relieved by TLX (SET), within the RARbeta2 promoter region which confers TLX- and RA-dependent transactivation [7].

Biological context of NR2E1

• A high degree of conservation across NR2E1 combined with a lack of interspersed repeats suggests that an array of regulatory elements embedded within the gene is required for proper gene expression [1].
• Because no artificial promoter was used to drive transgene expression, promoter and regulatory elements within the human NR2E1 clone are functional in mouse [2].
• Heterologous sera raised to human trophoblast (TLX antisera) have been shown to recognize peripheral blood lymphocytes (PBL); in unrelated studies noncytotoxic Fc receptors blocking B lymphocyte antibodies have been found in the sera of women during normal pregnancies [8].
• Evidence id presented for the presence of trophoblast-lymphocyte cross-reaction (TLX) cell surface antigens [9].
• 2. Allotypic seminal plasma TLX antigens may provide the antigenic stimuli for persistent maternal humoral immunity [10].

Anatomical context of NR2E1

• NR2E1 mRNA was detected in the adrenal gland, brain, cerebellum, testis, placenta, and bone marrow [11].
• Retina cells exhibit a far higher sensitivity to RA than do fibroblasts or osteoblasts, a property we found likely due to expression of the orphan nuclear receptor TLX [7].
• It has been proposed that allotypic trophoblast lymphocyte cross-reactive (TLX) antigens are involved in the maintenance of normal human reproduction [12].
• Patients with frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03) scans [13].
• The presence of TLX antigens in seminal plasma suggests that sensitization can occur before fertilization and implantation [14].

Associations of NR2E1 with chemical compounds

• Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX [7].
• The strong staining of the TLX antigens with Coomassie Brilliant Blue and Amido Black indicates they are largely proteins [12].
• Analysis of split ejaculates and immunohistological examinations of male accessory gland tissues showed the luminal epithelium of seminal vesicles as the source of seminal plasma TLX antigens [14].

Regulatory relationships of NR2E1

• TLX is predominately expressed in the brain and maps to RMD-2 at 6q21 between DNA markers FYN and D6S447, in a YAC clone that also contains marker D6S246 [3].

Analytical, diagnostic and therapeutic context of NR2E1

• Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans [13].
• The most potent antigen on the placenta is a class I molecule different from the classical transplantation antigens: Pa in the rat and TLX in the human [15].
• Xenogeneic anti-TLX sera were studied with the use of enzyme-linked-immunosorbent (ELISA) and immunochemical assays to determine the TLX status of seminal plasma [10].
• Well-defined monoclonal antibodies directed against HLA class I and class II molecules as well as beta 2-microglobulin and a TLX molecule were used in a standard indirect immunofluorescence test and some immunogold techniques at the electron microscopic level [16].
• As additional therapy, stent insertion and peripheral (Aa. poplitea Tll/tibial) angioplasty was performed (4 patients per group) [17].

References