Extra gene makes mice manic

Amanda Mascarelli in Nature:

Web-134104964Duplication of a single gene — and too much of the corresponding protein in brain cells — causes mice to have seizures and display manic-like behaviour, a study has found. But a widely used drug reversed the symptoms, suggesting that it could also help some people with hyperactivity who do not respond to common treatments. Smooth functioning at the synapses, the junctions between brain cells, is crucial to functions that control everything from social etiquette to everyday decision-making. It is increasingly thought that some neuropsychiatric disorders are caused by function of the synapses going awry1, and indeed researchers have found that neuropsychiatric conditions such as schizophrenia and autism can sometimes be traced to missing, mutated or duplicated copies of SHANK32, a gene that encodes one of the 'architectural' proteins that help to ensure that messages are relayed properly between cells. Some people with attention deficit hyperactivity disorder (ADHD), Asperger's syndrome or schizophrenia have an extra copy of a wider region of DNA that contains SHANK33.

To explore the role of SHANK3, Huda Zoghbi, a neurogeneticist at Baylor College of Medicine in Houston, Texas, and her colleagues created mice with duplicate copies of the gene. “The mouse was remarkably hyperactive, running around like mad,” says Zoghbi. But the animals did not respond to stimulant medications typically used to treat ADHD. Instead, their hyperactivity grew much worse. “That’s when we knew this was not typical ADHD,” says Zoghbi. The study is published today in Nature4. The paper is a “really good example of the importance of gene dosage”, says Thomas Insel, director of the US National Institute of Mental Health in Bethesda, Maryland. “It matters a lot whether you have no copies, one copy, two copies” or more of a given gene, he says.

More here.