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

Julia Panov, Hanoch Kaphzan

Research output: Contribution to journalArticlepeer-review


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 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.

Original languageEnglish
Article number105180
Number of pages14
JournalNeurobiology of Disease
StatePublished - Jan 2021

Bibliographical note

Publisher Copyright:
© 2020 The Authors


  • Angelman syndrome
  • Calcium signaling
  • Calcium-regulating genes
  • Calcium-target genes
  • RNA sequencing
  • Transcriptome
  • Humans
  • Male
  • Neuroblastoma/metabolism
  • Gene Knockdown Techniques
  • Calcium/metabolism
  • Female
  • Disease Models, Animal
  • Calcium Signaling/genetics
  • Angelman Syndrome/genetics
  • Computational Biology
  • RNA, Messenger/metabolism
  • Animals
  • Sequence Analysis, RNA
  • Neurons/metabolism
  • Hippocampus/metabolism
  • Sex Factors
  • Cell Line, Tumor
  • Mice
  • Induced Pluripotent Stem Cells
  • Ubiquitin-Protein Ligases/genetics

ASJC Scopus subject areas

  • Neurology


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