Ager-flox Mouse

AGER, also known as the receptor for advanced glycation end-products (RAGE), is a cell-surface transmembrane multiligand receptor encoded by the AGER gene. It is mainly expressed in the lung and is involved in multiple pathways such as NFκB, Akt, p38, and MAP kinases, which initiate and perpetuate a pro-inflammatory state [2].

In pancreatic ductal adenocarcinoma (PDAC) driven by the KRAS-G12D mutation, up-regulation of AGER in cancer cells instigates macropinocytosis, facilitating the internalization of serum albumin and subsequent amino acid generation for antioxidant glutathione synthesis, leading to resistance to the KRAS-G12D inhibitor MRTX1133 [1].

In sepsis, AGER-mediated lipid peroxidation drives caspase-11 inflammasome activation in macrophages, and inhibition of the AGER-ALOX5 pathway or depletion of AGER in myeloid cells protects against lipopolysaccharide-induced septic death in poly(I:C)-primed mice [3].

In cervical cancer, blockage of AGER with siRNAs suppresses proliferation, stimulates apoptosis, and inhibits migration, while overexpression of AGER has the opposite effects, suggesting it functions as a tumor promoter [4].

In juvenile idiopathic arthritis, the homozygous AA rs1035798 genotype of the AGER gene is a risk factor, and allele A is also associated with the disease as well as with the articular syndrome of non-autoimmune etiology [5].

In conclusion, AGER plays crucial roles in various biological processes and disease conditions. Its functions in inflammation, apoptosis, immunity, and cancer progression are revealed through different research models. The study of AGER in gene knockout or conditional knockout mouse models, as well as other functional studies, provides insights into the molecular mechanisms underlying diseases like PDAC, sepsis, cervical cancer, and juvenile idiopathic arthritis, which may help develop new therapeutic strategies.