Psychotic mice used to study disease

Tuesday, August 31, 2004 Posted: 9:37 AM EDT (1337 GMT)

WASHINGTON (Reuters) -- Psychotic mice that flee their littermates may offer insights into diseases such as schizophrenia, U.S. researchers reported on Monday.

The genetically engineered mice have mutations in two key genes that make them psychotic, the team at University of Texas Southwestern Medical Center and Children's Hospital Medical Center in Cincinnati found.

The mutations are the same as those found in a Canadian family with a history of schizophrenia, and involve two poorly understood genes, the researchers said.

"These mice display certain deficits that are potentially consistent with schizophrenia," said Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and leader of the study.

The genes are called NPAS1 and NPAS3. The researchers mated mice that were genetically engineered to lack copies of the gene and watched the behavior of their offspring.

Those that lacked any working copy of NPAS3 were especially erratic, the researchers report in this week's issue of the Proceedings of the National Academy of Sciences.

Normally, caged mice will climb over and sniff one another, but the mice with the genetic mutations failed to socialize. One small group of the mutant mice darted around wildly, avoiding their siblings.

Both NPAS genes are expressed, or active, in brain cells called inhibitory interneurons. They control transcription factors, which are proteins that can activate or deactivate other genes. Just which genes they may control is unclear, McKnight said.

More than 2 million Americans have schizophrenia, according to the National Institute of Mental Health. The disease, which usually shows up in early adulthood, affects a patient's ability to manage emotions, interact with others and think clearly.

Patients may suffer hallucinations, delusions and disordered thinking and have a high risk of suicide. Drugs can manage the symptoms but have unpleasant side effects.

Other researchers have found genetic links to schizophrenia as well.

McKnight's team said when they examined the brains of the psychotic mice, they found abnormally low levels of a protein called reelin. Reelin is important in the embryonic development of the brain and later in life to brain cell signaling.

Other studies of people who died with with schizophrenia have found reduced levels of reelin in their brains.