Autism recreated in mice, known as Shank3 mutants

Mice with a mutation in the Shank3 gene show autistic behaviors and impaired communication between brain cells. They could be a platform for future testing.

By fashioning a single mutation in the brain, scientists have recreated autistic behaviors in mice.

That gene is known as Shank3, and it codes for a protein that can interfere with the communication between brain cells.

And it’s been previously implicated in many cases of autism spectrum disorder (ASD) – which is partly characterized by repetitive behaviors and avoidance of social interaction. About one in 110 children in the US have the condition.

There are no effective treatment drugs at the moment, but Shank3 mutants could allow ways to assess experimental autism drugs before they're tested in humans.

Guoping Feng and the team of Duke and MIT researchers created the mice with Shank3 gene deletions.

  • These mice exhibited self-injurious repetitive grooming and avoided social interactions with other mice.
  • Their brains had defects in the striatum – which is involved in motor activity, decision-making, and certain aspects of behavior.
  • There were also defects in the circuits that connect the striatum and the cortex.

Healthy connections between these areas are key to effective regulation of social behaviors and interaction.

Because Shank3 is found at synapses (the junctions between brain cells), it helps neurons communicate with each other. MIT news explains:

At a synapse, one cell sends messages by releasing chemicals called neurotransmitters, which interact with the cell receiving the signal (known as the postsynaptic cell). This signal provokes the postsynaptic cell to alter its activity in some way – for example, turning a gene on or off. Shank3 is a ‘scaffold’ protein, meaning that it helps to organize the hundreds of other proteins clustered on the postsynaptic cell membrane, which are necessary to coordinate the cell’s response to synaptic signals.

“We now have a very robust model with a known cause for autistic-like behaviors,” Feng says. “We can figure out the neural circuits responsible for these behaviors, which could lead to novel targets for treatment.”

Though only a small percentage of autistic patients have mutations in Shank3, Feng believes that many other cases may be caused by disruptions of other synaptic proteins.

If that turns out to be the case, it should be possible to develop treatments that restore synaptic function, Feng says, regardless of which particular synaptic protein is defective in the individual patient.

The study was reported in Nature yesterday.

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Image: mouse cleaning itself by Radagast via Flickr

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