New Findings on Myelin Mechanism Involved in Genetically Based Autism

By Jordana Jampel - Last Updated: November 26, 2024

SHANK3 gene mutations are associated with high risk for monogenic autism spectrum disorder (ASD), and the impact of these mutations have been extensively studied in neurons and at excitatory synapses.

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A research group led by Professor Boaz Barak and PhD student Inbar Fischer aimed to examine the effect of SHANK3 mutations on oligodendrocytes (OLs) and myelination. The study, published in Science Advances, expands the understanding of the biologic mechanism underlying genetically based autism.

The research group used a genetically engineered mouse model for autism and introduced a mutation in the SHANK3 gene that mirrors that mutation found in humans with monogenic ASD. The researchers discovered that the specific mutation causes a dual impairment in the brain’s development and proper function.

The defective SHANK3 protein disrupts message transmission to vital support cells in oligodendrocytes. In addition, myelin production is disrupted, and as a result does not properly insulate neuronal axons, thus reducing the efficacy of electrical signal transmission between brain cells.

“Scientifically, we learned that defective myelin plays a significant role in autism and identified the mechanism causing the damage to myelin. Additionally, we revealed a new role for the SHANK3 protein: building and maintaining a functional binding substrate for receptors critical for message reception in oligodendrocytes (not just in neurons),” Professor Barak concluded.

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