Lectin Biomarker Development in a Mouse Model of GNE Myopathy

Abstract

GNE Myopathy (GNEM) is a rare autosomal recessive disease that causes progressive muscle wasting. GNEM occurs due to mutations in the GNE gene that encodes a key enzyme of the biosynthetic pathway of sialic acid, a terminal glycan on extracellular chains of muscle cells. Mutations in the GNE gene cause a significant reduction in the production of sialic acid, which is associated with muscle weakness and wasting. In order to assess the cellular effects of sialic acid‐producing therapies in clinical studies, a robust biomarker is needed to quantify the levels of sialic acid in muscle. Several lectins have shown robust and replicable changes after sialic acid perturbations in human cells. However, the ideal lectin biomarker for GNEM would also need to reflect relevant sialic acid changes in mouse models of GNEM, which are used to test the efficacy of gene therapies during pre‐clinical studies. Here, we compare lectin staining in skeletal muscle of wild type mice and the GNED207VTgGne‐/‐ mouse model of GNEM. Validation of a biomarker in this mouse model can facilitate pre‐clinical studies of GNEM gene therapy in mice.