Induction of Interferon-Stimulated Genes and Cellular Stress Pathways by Morpholinos

The phenotypes caused by morpholino-mediated interference of gene function in zebrafish are often not observed in the corresponding mutant(s). We took advantage of the availability of a relatively large collection of transcriptomic datasets to identify common signatures that characterize morpholino-injected animals (morphants). In addition to the previously reported activation of tp53 expression, we observed increased expression of the interferon-stimulated genes (ISGs), isg15 and isg20, an extrinsic cell death pathway gene, casp8, and other cellular stress response genes including phlda3, mdm2 and gadd45aa. Studies involving segmentation stage embryos were more likely to show upregulation of these genes. We also found that these genes could be upregulated by an increasing dose of egfl7 morpholino, or high doses of standard control morpholino. Thus, these data suggest that morpholinos can stimulate the innate immune response in zebrafish, as was recently reported in Xenopus.