Here we established a transgenic mouse line that expresses GNE containing the sialuria mutation R263L, in order to investigate the influence of an altered sialic acid concentration on the organism.
Sialuria is a dominant disorder caused by missense mutations in the allosteric site of GNE, coding for the rate-limiting enzyme of sialic acid biosynthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase.
Mutations in the binding site of the feedback inhibitor CMP-sialic acid of the GNE leads to sialuria, a disease in which patients produce sialic acid in gram scale.
Mutations associated with sialuria are located in the epimerase domain, and those associated with IBM2 are in the epimerase or the kinase domain or both, whereas the mutations we observed in the Nonaka myopathy patients were located in the sugar kinase domain of the gene.