Ventricular size mapping in a transgenic model of schizophrenia

Genetically engineered mice have been generated to model a variety of neurological disorders. The chakragati (ckr) mouse is beginning to provide valuable insights into the structural brain changes underlying certain manifestations of schizophrenia. For instance, these mice show enlargement of the lateral ventricles, an abnormality frequently reported as a structural aberration in the schizophrenic brain. As neither the anatomical pattern nor the timing of this ventricular enlargement is known, we used magnetic resonance imaging (MRI) techniques to non-invasively visualize the development of the ventricular system in 5-, 10- and 30-day-old ckr pups. High-resolution MR images obtained from these mutants showed a progressive enlargement of the lateral ventricles, starting at day 5 of postnatal life. These emerging deficits were associated with abnormalities in mid-saggital corpus callosum area and thickness, particularly in 30-day-old adolescent animals. At this time of development, aberrant behaviors that mimic certain symptoms of schizophrenia also appeared in ckr mice suggesting that structural changes in ventricular size predates the onset of psychotic-like behaviors. These results are viewed as further indication that pre- and peri-natal disturbances of the ventricular system and adjacent neural regions may be important pathogenic factors in schizophrenia. Application of MRI to the ckr mouse is relatively new but has great potential for clarifying the relationship between brain structure changes and genetically induced vulnerabilities to psychoses.