Signatures of altered gene expression in dorsal root ganglia of a Fabry disease mouse model

In the current study we performed mRNA microarray expression profiling of DRG samples from α-Gal A(-/0) mice aged >20 weeks when the disease is fully developed to investigate the mRNA signatures associated with FD peripheral nerve neuropathy. We found that in total 812 genes from the overall 21’736 detected mRNAs were significantly different between DRG samples from wildtype and α-Gal A(-/0) mice (criteria p ≤ 0.01, absolute fold change ≥ 1.2). Of those, 506 genes were significantly upregulated and 306 genes were significantly downregulated as compared to wildtype controls. More stringent filtering (criteria p ≤ 0.01, absolute fold change ≥ 2) of those significantly regulated genes revealed an assessable number of 78 genes in total. Using these criteria 41 genes were significantly upregulated, of which 29 showed FDR corrected p-values ≤ 0.1. Furthermore, 31 genes remained significantly downregulated, of which 27 showed FDR corrected p-values ≤ 0.1. Genome-wide expression profiling was carried out by IMGM Laboratories (Munich, Germany) using Agilent SurePrint G3 Mouse GE 8x60K Microarrays in combination with a one-color based hybridization protocol on lumbar DRGs L3-L5 from α-Gal A(-/0) and wildtype controls. Eight adult mice per group were deeply anesthetized with isoflurane and euthanized by decapitation. Spinal cords were removed, lumbar DRGs L3-L5 harvested and flash-frozen in liquid nitrogen. The DRG tissue from two mice was pooled for the final tissue sample.