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.