Are zebrafish the key to finding the cure for autism?

Published June 19, 2012

| FoxNews.com

Scientists may have found a powerful tool in the fight against autism – the zebrafish.

A team of researchers at MIT focused on a group of two dozen genes that have been found to be either missing or copied in about one percent of patients with autism.  Their study revealed that when they deleted these genes from zebrafish embryos, nearly all the fish developed brain abnormalities.

The findings – published in the online edition of the journal Disease Models and Mechanism – are significant because fish are incapable of showing symptoms of autism and other human brain disorders.  According to the researchers, their results could help to locate genes for further research in mammals.

“That’s really the goal – to go from an animal that shares molecular pathways, but doesn’t get autistic behaviors, into humans who have the same pathways and do show these behaviors,” said Hazael Sive, associate dean of MIT’s School of Science as well as the study’s lead researchers.

The genetic region the Sive and her team focused on is known as 16p11.2 – which includes 25 genes with yet unknown functions.  A normal genome consists of two copies of every gene, one from the father and one from the mother.  Variants occur when one copy is deleted or duplicated.  Deletion or duplication of genomes in the “core” 16p11.2 region have known to be associated with autism

Once the researchers found the genes in the zebrafish equivalent to the genes in the 16p11.2 area, they studied each gene at a time and eventually ‘silencing’ them by stopping their binding proteins from being produced.

When silenced, 21 of the 25 genes caused abnormal brain development – including thinning of the brain or inflammation of the brain ventricles.  The team also found abnormalities in the wiring of axons – neural projections responsible for carrying messages to the neurons.

To further demonstrate the importance of the gene region in the development of the brain, the researchers were even able to reverse the brain abnormalities in the fish by treating them with the human equivalents of the genes that had been silenced.

“That allows you to deduce that what you’re learning in fish corresponds to what that gene is doing in humans. The human gene and the fish gene are very similar,” Sive said.

The next step involves discovering which genes have a significant impact on the diagnosis of autism.  Sive’s lab will further their research by working with Stanford University to explore if the predictions they made in the zebrafish hold true in mice.

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