Bioinformatics analyses show dysregulation of calcium-related genes in Angelman syndrome mouse model.

Abstract Background Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by the loss of function of the UBE3A protein in the brain. In a previous study, we showed that activity-dependent calcium dynamics in hippocampal CA1 pyramidal neurons of AS mice is compromised, and its normalization rescues the hippocampal-dependent deficits. Therefore, we expected that the expression profiles of calcium-related genes would be altered in AS mice hippocampi. Methods We analyzed mRNA sequencing data from AS model mice and WT controls in light of the newly published CaGeDB database of calcium-related genes. We validated our results in two independent RNA sequencing datasets from two additional different AS models: first one, a human neuroblastoma cell line where UBE3A expression was knocked down by siRNA, and the second, an iPSC-derived neurons cell line from AS patient and healthy donor control. Findings We found signatures of dysregulated calcium-related genes in AS mouse model hippocampus. Additionally, we show that these calcium-related genes function as signatures for AS in other human cellular models of AS, thus strengthening our findings. Interpretation Our findings suggest the downstream implications and significance of the compromised calcium signaling in Angelman syndrome. Moreover, since AS share similar features with other autism spectrum disorders, we believe that these findings entail meaningful data and approach for other neurodevelopmental disorders, especially those with known alterations of calcium signaling. Funding This work was supported by the Angelman Syndrome Foundation and by the Israel Science Foundation, Grant Number 248/20.