The engineered mice with a specific gene deletion acted completely different from normal mice, according to the researchers.
Credit: Veer Images
This three-dimensional representation of the mouse brain highlights eight regions (shown with different colors) affected by 16.p11.2 deletion.
Credit: Mills/CSHL
WASHINGTON: Autistic mice have been engineered through the deletion of a specific cluster of genes in a study that could lead to improved diagnosis and treatment of the disease.
Some children with autism have a small deletion on chromosome 16, affecting 27 genes, so scientists at Cold Spring Harbour Laboratory in New York tried to alter mice to have the same genetic mutation.
By generating mouse models of autism using a technique known as chromosome engineering, the research team has provided the first functional evidence that inheriting fewer copies of these genes leads to features resembling those used to diagnose children with autism.
"Children normally inherit one copy of a gene from each parent. We had the tools to see whether copy number changes found in kids with autism were causing the syndrome," said Alea Mills, co-author of the study published in the Proceedings of the National Academy of Sciences today. "The idea that this deletion might be causing autism was exciting. So we asked whether clipping out the same set of genes in mice would have any effect."
Explains infant death?
Previous studies have suggested genetic causes could be to blame for the developmental disorder, which can cause social awkwardness, repetitive movements, sensitivity to certain lights and sounds, as well as behavioural problems.
The researchers found that the altered mice showed similar behaviours, including hyperactivity, trouble sleeping and difficulty adapting to new environments. "Mice with the deletion acted completely different from normal mice," said co-author Guy Horev.
The researchers also found that about half the autistic mice died shortly after birth. They said that future studies could shed light on whether the genetic deficit could be linked to unexplained infant death.
Inventing diagnosis methods
By closely examining the mice brains with MRI scans, the researchers were able to identify which regions are altered in the autistic mice. Children who have autism, a range of disorders linked to abnormal brain chemistry, are typically diagnosed by age three. Boys are three to four times more likely to have autism than girls.
"Mills has created a valuable resource for everyone engaged in autism research. The technical skill is extraordinary in creating mouse models bearing a human genetic variant that has been associated with autism," commented Gerald Fischbach, director of Life Sciences and Simons Foundation Autism Research Initiative in New York.
It is hoped that the mice will help scientists to pinpoint the genetic basis of autism and elucidate how these alterations affect the brain. They could also be used for inventing ways to diagnose children with autism before they develop the full-blown syndrome, as well as for designing clinical interventions.
