Altered gene expression in prefrontal cortex of a Fabry disease mouse model

In the current study we performed mRNA microarray expression profiling of PFC samples from α-Gal A(-/0) mice aged >20 weeks when the disease is fully developed to investigate the mRNA signatures associated with FD cognitive symptoms. We found that in total 381 genes from the overall 21’393 detected mRNAs were significantly different between PFC samples from wildtype and α-Gal A(-/0) mice (criteria p ≤ 0.01, absolute fold change ≥ 1.2). Of those, 135 genes were significantly upregulated and 246 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 50 genes in total . Using these criteria 19 genes were significantly upregulated, of which 11 showed FDR corrected p ≤ 0.1. Furthermore, 31 genes were significantly downregulated, of which 17 showed FDR corrected p ≤ 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 PFCs from α-Gal A(-/0) and wildtype controls. Four adult mice per group were deeply anesthetized with isoflurane and euthanized by decapitation. Brains were removed, PFCs harvested and flash-frozen in liquid nitrogen.