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Mutant mice show key autism traits

While the causes of autism remain complex and mysterious, researchers are steadily adding pieces to its intricate puzzle. In what they believe to be a significant new approach to understanding "autism spectrum disorders" (ASD), researchers have developed a mouse that shows abnormal social interactions and brain hypertrophy characteristic of the disease.

In an article in the May 4, 2006, Neuron, Luis Parada and his colleagues report the results of removing (knocking out) a single gene associated with brain disorders in mice. The gene, called Pten, had been associated with a broad array of such disorders when knocked out throughout the animals' bodies. However, Parada and colleagues engineered mice to knock out the gene only in mature, or "postmitotic," neurons of the cerebral cortex and hippocampus in the brain. These regions are associated with higher brain function such as learning and memory.

The mutant mice showed major abnormalities in a variety of social interactions normally undertaken in mice, found the researchers. For example, they were far less likely to approach and sniff new mice introduced into their cage, compared to normal mice. And while normal mice show markedly less interest when such new mice are later reintroduced, the mutant mice did not show such a reduction in interest. This abnormality indicated "impaired social learning or inability to identify the juvenile due to the low level of initial interaction," wrote the researchers.

In other tests of social behavior, the researchers found that--when given the choice of investigating a cage holding another mouse or an empty cage--the mutant mice showed similar preference for the two. Normal mice by far prefer investigating the caged mouse.

The researchers also found the mutant mice to be deficient in nest-forming and sexual and maternal behavior. In tests of their reaction to such sensory stimuli as bright environments, the mutant mice showed hyperactivity and increased
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Source:Cell Press


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