Similar transcriptomic alterations in Cx43 knockdown and knockout astrocytes

Abstract

Previous findings of widespread transcriptomic alteration in tissues from connexin null mice raise the issue of whether the transcriptomic changes are directly due to connexin down-regulation or to "compensatory" developmental alterations for the missing gene. To start addressing this question, the authors compared with wild-type control the gene expression profiles of connexin43 (Cx43) knockout and Cx43siRNA knockdown wild-type cortical astrocytes. Array analysis revealed remarkable parallelism of transcriptomic changes in knockout and knockdown astrocytes, with similarly altered genes being located on all chromosomes and encoding proteins involved in a wide diversity of cell functions. Moreover, gene expression variability was analogously higher in Cx43 null and siRNA-treated astrocytes, and expression interlinkages were similarly altered among a selected subset of genes. This highly significant overlap between transcriptomic alterations in Cx43 knockout and knockdown astrocytes suggests that the widespread changes more likely reflect connexin-dependent Gene Regulatory Networks rather than developmental compensation for the missing gene.