Investigating Autism-linked Mitochondrial and Social Behavioural Deficits: MFN2 Knockdown in Zebrafish and Rescue by Human MFN2 Genes

Authors

  • Raneem Salah Colonel By Secondary School, Ottawa, ON, Canada
  • Areej Mustafa Colonel By Secondary School, Ottawa, ON, Canada

DOI:

https://doi.org/10.18192/osurj.v5i2.7938

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition defined by impaired social interaction and repetitive behaviors (1). Emerging evidence suggests that mitochondrial dysfunction may be a contributor to ASD. Proper neuronal energy production is critical for synaptic function, which facilitates pro-social behavior. Mitofusin-2 (MFN2), a key regulator of mitochondrial fusion, shows reduced expression in ASD patients, and is associated with abnormal mitochondrial morphology that impairs ATP production. However, the direct causal link between MFN2-mediated mitochondrial dysfunction and autism-related social behavior remains unclear (2).

This study investigates the effects of MFN2 knockdown on neuronal energy and social behavior in zebrafish (Danio rerio), and whether human MFN2 expression can rescue these deficits. Zebrafish are widely used as a neurodevelopmental model because they possess conserved genetic pathways related to human neurological disorders and display quantifiable social behaviours such as shoaling. Additionally, their transparent embryos and rapid development allow efficient genetic manipulation and real-time observation of developmental effects. Zebrafish embryos will be divided into four groups: wild-type, sham-injected, MFN2 knockdown, and a knockdown group receiving human MFN2 mRNA for rescue. MFN2 knockdown will be achieved via antisense morpholino injection at the one-cell stage, with expression levels validated through quantitative polymerase chain reaction and Western blot. To assess the impact on cellular energy and sociality, neuronal ATP levels will be measured using a luminescent assay while social cohesion will be evaluated using shoaling behavioral assay with automated tracking software. The Average Inter-Individual Distance will be quantified as the primary metric of group cohesion.

It is hypothesized that MFN2 knockdown will impair mitochondrial fusion, leading to reduced neuronal ATP availability and disrupted pro-social behavior, while human MFN2 expression will restore both energy production and shoaling. By establishing MFN2 as a critical link between mitochondrial dynamics and sociality, this research will clarify the role of metabolic dysfunction in ASD, providing insights into potential molecular pathways for therapeutic intervention.

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Published

2026-06-17

Issue

Vol. 5 No. 2 (2026)

Section

Ottawa Science Innovation Challenge Abstracts

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