Reduction of the ATP-binding cassette sub-family C member 4 (ABCC4) related to the expression of autism spectrum disorder on Drosophila melanogaster model

Abstract

Autism spectrum disorders (ASDs) are complex neurodevelopmental disabilities that have core diagnostic features including impaired social interaction, language development, and interpersonal skills with repetitive and restrictive behaviors. Researching this type of disorder in terms of the molecular and cellular mechanism has met many difficulties because of the complexity in choosing and creating an experimental model organism. In Vietnam, most of the studies have focused on identifying the mutation relating to ASDs at in vitro level without any in-depth study at in vivo level. Drosophila melanogaster has been widely used as an advantaged model organism in classical and modern genetics for more than 100 years because its genome was small and simple but having homologues for at least 75% of human disease genes, thereby indicating that this has been an extremely excellent genetic model. Therefore, this study aimed to elucidate the physiological role of the ABCC4 gene mutant Drosophila model by specifically knocked down this protein in all neurons of these flies and investigated the deficiency of this gene in terms of autism features. The result exhibited that the interaction between individuals in the population was sharply reduced between the gene mutant carrier group and the control group. The knockdown of dABCC4 protein in all neurons induced early onset of evening activity and hyperactivity during morning peaks and evening peaks. The ABCC4 genetically modified flies had a rhythm sleep disorder compared to the wild-type flies (ABCC genes). These phenotypes were similar to defects observed in humans with autism spectrum disorder. These preliminary results have contributed to elucidate the role of this protein in the molecular mechanism of the autism.