July 30, 2007

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.”


Bloody amazing, I can see myself going down to the local pet shop and asking for a mutant mouse, preferably one that has schizophrenia.

Posted by: Salty Davis at July 30, 2007 12:55 PM

I would assume this is mostly a show business other than a truth. Just think of this:

There is currently no physical or lab test that can absolutely diagnose schizophrenia - a psychiatrist usually comes to the diagnosis based on clinical symptoms. (From http://www.schizophrenia.com/diag.php)

Even for a human, schizophrenia is diagnosed mainly by what the patient said and what the psychiatrist observed during an appointment. It is very hard to diagnose someone as schizophrenia when the patient doesn't tell the true symptoms (such as hearing voices and having visual hallucination).

I doubt how much confidence Dr. Sawa has when he claims these mice have "schizophrenia".

Posted by: JD05 at July 30, 2007 05:13 PM

Of course to talk of mice as fully schizophrenic would be an exaggeration, a journalist stunt to draw attention. What they mean is that these mice have an "endophenotype" - partial phenotype, a quantifiable set of traits (lack of Prepulse Inhibition, catalepsy, fear of open spaces, bad working memory, changes in the brain structure or metabolites; in the case of DISC1 - disrupted protein transport and PDE4B regulation) that copy those found in human patients. For example, a translocation in NPAS3 gene leads to severe and rare form of schizophrenia; NPAS3-deficient mice have a set of behaviours associated with mice models of the disease, and a significant trait - decrease in Reelin protein, which is also decreased in humans with schizophrenia. So they may serve as partial models, brain changes and their causes could be investigated. Naturally a mice would not hallucinate or create a delusional system of beliefs.

Posted by: CopperKettle at July 30, 2007 07:44 PM

Hello. How are you today? My name is Mikhail Leonidovich Fayn, and, I have heard this amazing news just yesterday. I'm amazed by how far science has come to help mentally ill humans to finally get cured and end their mental illness torment that schizophrenia can be for me, as, I have it since 1994A.D.
My official diagnosis of it was given to me in Elmhurst General Hospital in Elmhurst Queens, New York City in the psychiatric adolescent unit at the age of 13, on Friday May 27th, 1994A.D. at 12:10P.M., Eastern U.S.A., time, and, this news has given me a ray of renewed hope that someday my chemical brain imbalance will be like that of a non-schizophrenic individual.
Sincerely, yours
Mikhail Leonidovich Fayn
P.S. I'll wait as long as it takes to cure the mentally ill mice, so, that one day all schizophrenic humans could be scientifically cured as, well.

Posted by: Mikhail Fayn at July 31, 2007 05:42 AM

A report about the mice has appeared at the Schizophrenia Research Forum website:

Modeling Schizophrenia Phenotypes—DISC1 Transgenic Mouse Debuts


Posted by: CopperKettle at August 2, 2007 10:28 PM

Mice with schizophrenia may seem a funny concept, and maybe a bit backwards. But let me ask you this: how on earth do you think potential treatment for mental disorders (such as schizophrenia) are tested? Drugs don't magically show up on the shelf, they must go through many many years of trials. A mouse model of the disease is a HUGE step forward in finding a cure...

Posted by: Emily at March 5, 2008 03:23 AM

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