RAGE (receptor for advanced glycation endproducts), also called AGER, is a transmembrane receptor of the immunoglobulin super family. Its name comes from its ability to bind advanced glycation endproducts (AGE), which include chiefly glycoproteins, the glycans of which have been modified non-enzymatically through the Maillard reaction. In view of its inflammatory function in innate immunity and its ability to detect a class of ligands through a common structural motif, RAGE is often referred to as a pattern recognition receptor. RAGE also has at least one other agonistic ligand: high mobility group protein B1 (HMGB1). HMGB1 is an intracellular DNA-binding protein important in chromatin remodeling which can be released by necrotic cells passively, and by active secretion from macrophages, natural killer cells, and dendritic cells. The interaction between RAGE and its ligands is thought to result in pro-inflammatory gene activation. Due to an enhanced level of RAGE ligands in diabetes or other chronic disorders, this receptor is hypothesised to have a causative effect in a range of inflammatory diseases such as diabetic complications, Alzheimer’s disease and even some tumors. Isoforms of the RAGE protein, which lack the transmembrane and the signaling domain (commonly referred to as soluble RAGE or sRAGE) are hypothesized to counteract the detrimental action of the full-length receptor and are hoped to provide a means to develop a cure against RAGE-associated diseases.
Gene targeting strategy for B-hRAGE mice. The exon 1~11 of mouse Rage gene that encode the full-length protein were replaced by human RAGE exon 1~11 in B-hRAGE mice.
Protein expression analysis
Strain specific analysis of RAGE expression in WT and B-hRAGE mice by western blot. Lung were collected from WT mice and heterozygous B-hRAGE (H/+) mice. Mouse RAGE was detectable in WT mice and heterozygous B-hRAGE. Human RAGE was exclusively detectable in heterozygous B-hRAGE but not WT mice.