Three Genes in the Human MHC Class III Region near the Junction with the Class II: Gene for Receptor of Advanced Glycosylation End Products, PBX2 Homeobox Gene and a Notch Homolog, Human Counterpart of Mouse Mammary Tumor Gene int-3

Effects of Novel Polymorphisms in the RAGE Gene on Transcriptional Regulation and Their Association With Diabetic Retinopathy

“…The localization of these polymorphisms to the correct loci was complicated by our finding that part of the RAGE 5Ј flanking region was duplicated on another chromosome. PBX2, the gene 5Ј to RAGE, has its 3ЈUTR overlapping with part of the RAGE 5Ј regulatory region (6). The PBX2 gene has a pseudo-copy on chromosome 3 (22); however, two independent studies using fluorescent in-situ hybridization have shown RAGE to be solely located on chromosome 6 (6,23).…”

“…The receptor most supported by studies is RAGE, a member of the immunoglobulin superfamily. The gene for RAGE is found on chromosome 6p21.3 in the MHC locus and is composed of a 1.7-kb 5Ј flanking region and 11 exons (6). RAGE is normally expressed at low levels by the endothelium, smooth muscle, mesangial, and monocytes (7), but in both animal models and human diabetic subjects, high levels of RAGE expression have been identified in the retina, mesangial, and aortic vessels, concomitant with AGE accumulation (8,9).…”

“…To investigate for the presence of novel polymorphisms in the RAGE 5Ј flanking region, we screened the entire 5Ј gene regulatory region of RAGE for novel polymorphisms using a combination of single-strand conformation polymorphism (SSCP) and denaturing highperformance liquid chromatography (DHPLC). Because of the dense nature of genes within the MHC locus, part of the 5Ј flanking region of RAGE overlaps with the 3Ј untranslated region (UTR) of the PBX2 gene (6), further complicating the correct identification of polymorphisms due to the presence of a pseudogene copy of PBX2 on chromosome 3. Correctly identified polymorphisms were functionally characterized by transient transfection assays using RAGE promoter regions to drive the chloramphenicol acetyl transferase (CAT) reporter gene, and nuclear protein interactions were characterized by electrophoretic mobility shift assays (EMSA).…”

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response

“…Further analyses were performed to account for the linkage disequilibrium described previously between RAGE 82S and an RA-associated allele, HLA-DRB*0401. 9,[32][33][34] To assess whether the RAGE 82S allele confers risk independent of DRB1*0401, we compared the frequency of the RAGE 82S allele in 0401+ patients and controls.…”

Proto‐oncogene of int‐3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis

“…6 MHC region (Sugaya et al 1994). To clone a novel mouse Notch homologue, we screened a mouse genomic library under low strigency using human genomic fragments as probes, and obtained a number of clones.…”