Schizophrenia Daily News Blog

Mice with Schizophrenia Created for Research

Scientists at Johns Hopkins University School of Medicine in Baltimore, Maryland have recently breed mice they believe to have "schizophrenia". This may be the first time an animal model was genetically engineered to have a mental illness - though other researchers have made similar claims.

The goal of creating these mice with schizophrenia is to allow scientist the opportunity to develop and test new treatments that can potentially be used in humans someday. This is a common approach for research into human diseases and has resulted in many new therapies for heart disease, obesity, and many more diseases and disorders.

Research for new drug treatments is often difficult and takes many years to be seen as safe enough for human trails. Having these mice can potentially speed up the process of future drug treatment trails.

"We can use them to explore how external factors like stress or viruses may worsen symptoms," said Dr. Akira Sawa of Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr. Akira Sawa recently received the NARSAD Staglin Prize for his work on the genetics of schizophrenia and specifically "having demonstrated that changes in the DISC1 gene that have been found in some families with major mental illnesses cause a defect in fundamental aspects of brain development."

The mice were created by modifying their DNA to "mimic a mutant gene (DISC1) first found in a Scottish family with a high incident rate of schizophrenia. The mice's brains were found to have similar features to those of humans with the disease, such as depression and hyperactivity."

"These mutant mice may provide an important new tool for further study of the combinations of factors that underlie mental illnesses like schizophrenia and mood disorders," said Takotoshi Hikida, of Johns Hopkins University in Baltimore, a leading researcher.

The DISC1 gene is just one of about a dozen or so key genes that are thought to play a key role in risk for developing schizophrenia (though environmental factors are also involved in increasing risk, or triggering the disorder) - so we suspect that additional research will be needed to develop mice that have all the same characteristics of schizophrenia that humans experience.

In contrast to current animal studies that rely on drugs that can only mimic the manifestations of schizophrenia, such as delusions, mood changes and paranoia, this new mouse is based on a genetic change relevant to the disease. Thus, this mouse should greatly help with understanding disease progression and developing new therapies.

Animal models of schizophrenia have been hard to design since many different causes underlie this disease. However, Akira Sawa, M.D., Ph.D., associate professor of psychiatry and neuroscience and director of the program in molecular psychiatry and his colleagues took advantage of the recent discovery of a major risk factor for this disease: the DISC1 gene (short for disrupted in schizophrenia), which makes a protein that helps nerve cells assume their proper positions in the brain.

As reported online this week in Proceedings of the National Academy of Sciences, the researchers generated mice that make an incomplete, shortened form of the DISC1 protein in addition to the regular type. The short form of the protein attaches to the full-length one, disrupting its normal duties.

As these mice matured, they became more agitated when placed in an open field, had trouble finding hidden food, and did not swim as long as regular mice; such behaviors parallel the hyperactivity, smell defects and apathy observed in schizophrenia patients. Magnetic resonance imaging (MRI), taken in collaboration with Susumu Mori, Ph.D., professor of radiology, also revealed characteristic defects in brain structure, including enlarged lateral ventricles, a region that circulates the spinal fluid and helps protect against physical trauma.

Sawa notes that the defects in these mice were not as severe as those typically seen in people with schizophrenia, because more than one gene is required to trigger the clinical disease. “However, this mouse model will help us fill many gaps in schizophrenia research,” he says. “We can use them to explore how external factors like stress or viruses may worsen symptoms. The animals can also be bred with other strains of genetically engineered mice to try to pinpoint additional schizophrenia genes.”