Mice with a gene mutation linked to rare human cases of autism show a characteristic symptom of the disease: impaired social interaction. The discovery, published online today in Science adds to recent evidence that defects in synaptic connections between neurons may contribute to autism and related disorders.
Autism is a generalized disorder characterized by social and communication problems and obsessive or repetitive behavior. Scientists do not know what causes it, but genetics seem to be important. Changes in several genes have been implicated. For example, a 03 study identified a mutation - a single switch letter in the genetic code for a protein called neuroligin-3 - two Swedish brothers, one with autism and one with the related Asperger but softer. Neuroligin-3 lies at synapses, communication points between neurons, but little is known about its function, much less how it contributes to the symptoms of autism.
To study, researchers led by Katsuhiko Tabuchi and Thomas Südhof at the University of Texas Southwestern Medical Center in Dallas created a strain of mice with the same mutation found in Swedish brothers. The mutant mice had normal activity and coordination, but when researchers have mutant mice in a chamber with a mouse that had been held in a small cage, they were unusually shy, spend less time sniffing and interact with mouse cage that normal mice did. (The mouse has been withheld, because otherwise it would have initiated interactions with mutants, confusing the test.) However, there was no difference between the mutant and normal mice when it came to inquire into an empty cage, and even normal mouse mutants outperformed on a spatial learning and memory test, suggesting that the deficit was specific to social behavior.
then, the team examined Südhof slices of brain tissue of mutant mice. A neuron typically receives a variety of synaptic inputs from its neighbors: some that turn to send a message and others that inhibit this communication. inhibitory signaling was unusually high in the mutant mice, the researchers found. Much more work is needed to understand why the mutation impairs the inhibitory signaling and, in turn, how it could affect social behavior, said Südhof. Although, he said, the findings suggest that "the synapse is where things happen." Other recent work Südhof and others also points in this direction ( Science , July 13).
"This is really the science done well," said Daniel Geschwind, Neurogeneticist at the University of California, Los Angeles, adding that the mouse should be useful for further studies on autism. Huda Zoghbi, a geneticist at Baylor College of Medicine in Houston, Texas, agrees: "It's a great mouse to start looking," she said Geschwind Yet, Zoghbi and others caution that the findings. current may not apply to all cases of autism. Extremely small number of human cases of the disease are caused by mutated genes for neuroligin and related proteins, says Edwin Cook, an autism researcher at the University of Illinois Medical Center in Chicago. "We do not know how this mechanism will generalize," Cook said.
Related Sites
- Information on autism NINDS
- science section on the role of synaptic proteins and autismlike disorders
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