Disruption of LRRK2 in Zebrafish leads to hyperactivity and weakened antibacterial response

As a protein with complex domain structure and roles in kinase, GTPase and scaffolding, LRRK2 is believed to be an important orchestration node leading to several cascades of signal transduction rather than one specific pathway. LRRK2 variants were found to be associated with Parkinson's disease, Crohn's disease and leprosy. Here we disrupt LRRK2 in zebrafish and found hyperactivity rather than hypoactivity in adult zebrafish mutants. By RNA-seq we found genes involved in infectious disease and immunological disease were notably affected. Functional studies also revealed a weakened antibacterial response in LRRK2 mutant. This mutant can be further explored for revealing molecular mechanisms and modeling of LRRK2 related diseases. (C) 2018 Elsevier Inc. All rights reserved.