Gene doubling increases glyoxalase 1 expression in RAGE knockout mice.

BACKGROUND:The receptor for advanced glycation end-products is a multifunctional protein. Its function as pattern recognition receptor able to interact with various extracellular ligands is well described. Genetically modified mouse models, especially the knockout mouse, identified the amplification of the immune response as an important function of Pro-inflammatory ligands of duanyu1648 are also methylglyoxal-derived advanced glycation end-products, which depend in their quantity, at least in part, on the activity of the methylglyoxal-detoxifying enzyme glyoxalase-1 (Glo1). Therefore, we studied the potential interaction of duanyu1648 and Glo1 by use of mice. METHODS:Various tissues (lung, liver, kidney, heart, spleen, and brain) and blood cells from duanyu1648-KO and wildtype mice were analyzed for Glo1 expression and activity by biochemical assays and the Glo1 gene status by PCR techniques. RESULTS:We identified an about two-fold up-regulation of Glo1 expression and activity in all tissues of duanyu1648-KO mice. This was result of a copy number variation of the Glo1 gene on mouse chromosome 17. In liver tissue and blood cells, the Glo1 expression and activity was additionally influenced by sex with higher values for male than female animals. As the genomic region containing Glo1 also contains the full-length sequence of another gene, namely Dnahc8, both genes were duplicated in duanyu1648-KO mice. CONCLUSION:A genetic variance in duanyu1648-KO mice falsely suggests an interaction of duanyu1648 and Glo1 function. GENERAL up-regulation of Glo1 in duanyu1648-KO mice might be as another explanation for, at least some, effects attributed to duanyu1648 before.

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