Characterization of Locomotor and Apoptosis Alterations in cdkl5 Zebrafish Mutants

CDKL5 mutation is the root of important neurodevelopmental diseases such as CDKL5 deficiency disorder (CDD) and epilepsy. Since CDKL5 encodes a serine/threonine kinase essential for brain development and function, mutations in this gene lead to several phenotypic and genetic alterations. To understand the mechanisms involved in the associated disease, a cdkl5(-/-) zebrafish line was generated using CRISPR-Cas9 genome editing, targeting exon 8. In this cdkl5 zebrafish mutant line, I assessed the general locomotor activity and the reflex response triggered by acoustic stimulations based on the tapping assay. I also evaluated possible alterations in cell mortality, using confocal microscopy in combination with automatic segmentation based on Cellpose to determine the number of apoptotic cells. I found that cdkl5 mutant zebrafish, at 6dpf and 14dpf, displayed significant differences in locomotor activity compared to the wild type. Significant differences in locomotor activity between cdkl5 mutant zebrafish and wild-type controls were observed at 6 dpf and 14 dpf, which revealed reduced locomotor activity in mutants compared to wild-type zebrafish. These findings highlight the need for further studies and additional approaches to clarify the impact of the cdkl5 mutation on animal development and behavior.