Modeling Neurodevelopmental Disorders and Epilepsy Caused by Loss of Function of in Zebrafish.

In recent years there has been extensive research on malformations of cortical development (MCDs) that result in clinical features like developmental delay, intellectual disability, and drug-resistant epilepsy (DRE). Various studies highlighted the contribution of microtubule-associated genes (including tubulin and kinesin encoding genes) in MCD development. It has been reported that mutations in , a member of the family, are linked to brain malformations and DRE. Although it is known that KIF2A functions by regulating microtubule depolymerization via an ATP-driven process, implications of loss of function remain partly unclear. Here, we present a novel knock-out zebrafish model, showing hypoactivity, habituation deficits, pentylenetetrazole-induced seizure susceptibility and microcephaly, as well as neuronal cell proliferation defects and increased apoptosis. Interestingly, larvae survived until adulthood and were fertile. Notably, our zebrafish knock-out model demonstrated many phenotypic similarities to mouse models. This study provides valuable insights into the functional importance of in zebrafish and phenotypical hallmarks related to mutations. Ultimately, this model could be used in a future search for more effective therapies that alleviate the clinical symptoms typically associated with MCDs.