Scientists at Johns Hopkins have developed a mouse model for schizophrenia in which a mutated gene linked to schizophrenia can be turned on or off at will.
The researchers developed the transgenic mouse by inserting the gene for mutant Disrupted-In-Schizophrenia-1 (DISC-1) into a normal mouse, along with a promoter that enables the gene to be switched on or off. Mutant DISC-1 was previously identified in a Scottish family with a strong history of schizophrenia and related mental disorders.
The study was performed in the laboratory of Mikhail Pletnikov, M.D., Ph.D., in the Department of Psychiatry and Behavioral Sciences.
Last month, another Hopkins researcher in the Department of Psychiatry and Behavioral Sciences, Akira Sawa, M.D., Ph.D., and his team, developed a comparable mutant DISC-1 mouse model for schizophrenia. Pletnikov's is the first model in which researchers can control the expression of this mutated gene, and the model illuminates additional aspects of the biology of the disorder.
Researchers turn off the mutant DISC-1 gene by feeding the mice a nontoxic chemical that controls a genetically engineered switch mechanism to turn on production of the DISC-1 protein.
The study, which appears in the September issue of Molecular Psychiatry, showed that male mice with the mutant DISC-1 gene were significantly more active than control mice without the mutated gene. The investigators also observed that the male mutant DISC-1 mice had altered social interactions with other mice and were more aggressive. Females with the mutated gene had a more difficult time remembering how to navigate a maze.
“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,” says Pletnikov.
The research showed other strong similarities between the mouse model and humans with schizophrenia.
Examination of the brains of the mutated mice using MRI scans showed significant enlargement of the lateral ventricles (fluid-filled areas in the front of the brain), very similar to MRI findings in humans with schizophrenia.