'Schizophrenic' mouse points to genetic treatments

Wednesday, 2 July 2003 1:41 AM

A genetically engineered mouse, whose behaviour is strikingly similar to that of schizophrenics, has led scientists to identify a specific gene that predisposes humans to the disease, and may lead to new genetic treatments.

Mice altered to knock out the gene for the brain protein calcineurin, showed short-term memory problems, attention deficits and other abnormalities characteristic of schizophrenia, Nobel laureate Susumu Tonegawa from MIT and his team observed.

Before the behaviour of these calcineurin deficit mice was investigated, there was no evidence of a link between the protein and schizophrenia. But the animals chose to sleep separately and instead of nest building, scattered nesting materials about their cage - sparking the interest of researchers.

They used a human schizophrenia diagnostic test on the mice, in which a startling tone is broadcast to the subject, followed by a weaker tone. Normal mice and non-schizophrenic humans are less startled by the second tone, as they are prepared by the first. But these mice, like schizophrenic humans, were significantly more startled by the second tone.

The team then took DNA samples from schizophrenic patients and their immediate relatives and found an association between the particular calcineurin gene and schizophrenia.

"This is an intriguing series of findings," Dr Tonegawa said.

"The combination of evidence from the genetically altered mice, together with the human gene studies, create a strong argument to link calcineurin with schizophrenia."

It is hoped that the study, published this week in the online edition of the Proceedings of the National Academy of Sciences, may generate the first genetically targeted drugs for the disease, which affects 1% of the population worldwide.

It is already thought that alterations in collections of genes cause a predisposition to schizophrenia, and the team suspects that many of these genes may be linked to the calcineurin biochemical pathway in the brain, which has an important role in the central nervous system.

Once the genes are identified fully, researchers will be able to determine which brain proteins are affected by the disease allowing screening of a large number of potential drugs to treat schizophrenia.

It is hoped this will yield a new class of antipsychotic drugs that more precisely and effectively treat the disorder.

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