The protein β-catenin, which is encoded by the CTNNB1 gene, is involved in the Wnt signalling pathway and plays an important role in early neurological development. Deficiency of ß-catenin causes a rare CTNNB1 syndrome, which is characterized by impaired cognitive and motor development. Our aim was to increase the amount of cytosolic ß-catenin by inhibiting the activity of Axin, which is involved in the degradation of ß-catenin by the destruction complex. For this purpose, we used antisense oligonucleotides (ASOs) targeting the binding sites of the splicing complex on Axin RNA. Deletion constructs of Axin without selected exons were prepared and their expression, co-localisation with ß-catenin and their influence on ß-catenin activity in HEK293T cells were investigated by western blot, confocal microscopy, and flow cytometry, respectively. We designed short ASOs and tested their ability to induce exon skipping at the RNA level and their effect on endogenous levels of Axin and ß-catenin in HEK293T cells. We demonstrated that exon skipping was successfully induced by ASOs at the RNA level. Treatment with ASOs led to a decrease in endogenous Axin levels and an increase in endogenous β-catenin levels. Two variants of endogenous Axin were detected after treatment with ASO:eks5. These results suggest the possibility of developing a therapy for the treatment of CTNNB1 syndrome based on antisense technology.
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