PT - JOURNAL ARTICLE AU - Partoens, Michèle AU - De Meulemeester, Ann-Sofie AU - Giong, Hoi-Khoanh AU - Pham, Duc-Hung AU - Lee, Jeong-Soo AU - de Witte, Peter A. AU - Siekierska, Aleksandra TI - Modeling Neurodevelopmental Disorders and Epilepsy Caused by Loss of Function of <em>kif2a</em> in Zebrafish AID - 10.1523/ENEURO.0055-21.2021 DP - 2021 Sep 01 TA - eneuro PG - ENEURO.0055-21.2021 VI - 8 IP - 5 4099 - http://www.eneuro.org/content/8/5/ENEURO.0055-21.2021.short 4100 - http://www.eneuro.org/content/8/5/ENEURO.0055-21.2021.full SO - eNeuro2021 Sep 01; 8 AB - 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 de novo mutations in KIF2A, a member of the kinesin-13 family, are linked to brain malformations and DRE. Although it is known that KIF2A functions by regulating microtubule depolymerization via an ATP-driven process, in vivo implications of KIF2A loss of function remain partly unclear. Here, we present a novel kif2a 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, kif2a−/− larvae survived until adulthood and were fertile. Notably, our kif2a zebrafish knock-out model demonstrated many phenotypic similarities to KIF2A mouse models. This study provides valuable insights into the functional importance of kif2a in zebrafish and phenotypical hallmarks related to KIF2A mutations. Ultimately, this model could be used in a future search for more effective therapies that alleviate the clinical symptoms typically associated with MCDs.