David Baxter PhD
Late Founder
Schizophrenia Gene May Have On/Off Switch
by Madeline Vann
Sept 11, 2007
Working with a mouse model of schizophrenia, researchers believe they may have found the disease's genetic on/off switch.
Understanding how this gene works could lead to the development of better treatments, the team said.
Researchers at Johns Hopkins University, Baltimore, developed a mouse model for schizophrenia by inserting the mutant Disrupted-In-Schizophrenia (DISC-1) gene into a normal mouse, along with a promoter that allows the gene to switch on or off.
Mutant DISC-1 was identified in a Scottish family with a strong history of schizophrenia and related disorders. The researchers found they could turn the gene off by feeding the mice a nontoxic chemical that affects the production of DISC-1 proteins.
The team also observed that male mice with the mutated gene were more active and aggressive than other mice. The gene also appeared to alter the mice's social interactions, and females with the mutated gene were less able to remember how to get through a maze.
The mouse model is similar enough to schizophrenia in humans for the research to have implications for human mental illness, the scientists said.
"Schizophrenia is a human disorder, so we cannot say the symptoms displayed by the mouse model are schizophrenic. But they are in line with the kinds of behavioral changes we see in humans with schizophrenia," lead researcher Dr. Mikhail Pletnikov said in a prepared statement.
The researchers also examined the brains of the mutated mice using MRI scans. The scans showed significant enlargement of the lateral ventricles -- fluid-filled areas of the brain that are often enlarged in humans with schizophrenia.
The team also found abnormal brain cells in brain tissue from the part of the brain associated with schizophrenia.
The mutated mice also had abnormal levels of two proteins -- 25 kDa synaptosome-associated protein (SNAP-25) and lissencephaly-1, which are both known to be important to brain cell development and growth. Prior studies of human brain tissue has shown abnormal levels of SNAP-25 as well.
"This model supports the idea that schizophrenia is a disease associated with abnormal brain development," senior co-author of the study Dr. Christopher Ross said in a prepared statement. "Being able to regulate the timing of expression of the mutant protein provides an opportunity to study the timing and mechanism of specific abnormalities -- a tool that could eventually lead to the discovery of drugs that could potentially control or even prevent the disease," he said.
The study is published in the September issue of Molecular Psychiatry.
More information
To learn about schizophrenia, visit the National Alliance on Mental Illness.
by Madeline Vann
Sept 11, 2007
Working with a mouse model of schizophrenia, researchers believe they may have found the disease's genetic on/off switch.
Understanding how this gene works could lead to the development of better treatments, the team said.
Researchers at Johns Hopkins University, Baltimore, developed a mouse model for schizophrenia by inserting the mutant Disrupted-In-Schizophrenia (DISC-1) gene into a normal mouse, along with a promoter that allows the gene to switch on or off.
Mutant DISC-1 was identified in a Scottish family with a strong history of schizophrenia and related disorders. The researchers found they could turn the gene off by feeding the mice a nontoxic chemical that affects the production of DISC-1 proteins.
The team also observed that male mice with the mutated gene were more active and aggressive than other mice. The gene also appeared to alter the mice's social interactions, and females with the mutated gene were less able to remember how to get through a maze.
The mouse model is similar enough to schizophrenia in humans for the research to have implications for human mental illness, the scientists said.
"Schizophrenia is a human disorder, so we cannot say the symptoms displayed by the mouse model are schizophrenic. But they are in line with the kinds of behavioral changes we see in humans with schizophrenia," lead researcher Dr. Mikhail Pletnikov said in a prepared statement.
The researchers also examined the brains of the mutated mice using MRI scans. The scans showed significant enlargement of the lateral ventricles -- fluid-filled areas of the brain that are often enlarged in humans with schizophrenia.
The team also found abnormal brain cells in brain tissue from the part of the brain associated with schizophrenia.
The mutated mice also had abnormal levels of two proteins -- 25 kDa synaptosome-associated protein (SNAP-25) and lissencephaly-1, which are both known to be important to brain cell development and growth. Prior studies of human brain tissue has shown abnormal levels of SNAP-25 as well.
"This model supports the idea that schizophrenia is a disease associated with abnormal brain development," senior co-author of the study Dr. Christopher Ross said in a prepared statement. "Being able to regulate the timing of expression of the mutant protein provides an opportunity to study the timing and mechanism of specific abnormalities -- a tool that could eventually lead to the discovery of drugs that could potentially control or even prevent the disease," he said.
The study is published in the September issue of Molecular Psychiatry.
More information
To learn about schizophrenia, visit the National Alliance on Mental Illness.
