International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Bock NA
Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, Canada

Co-Authors: 1) Davidson L M, 1) Kovacevic N, 2) Lipina T V, 2) Roder J C, 1) Henkelman R M
Institutions: 1) Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, Canada 2) The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

We are developing an in vivo magnetic resonance imaging (MRI) screening method for identifying structural abnormalities in the brains of mice that have identified behavioural abnormalities. The screen is designed to image the entire brain in three dimensions with 156 micron isotropic resolution. The effective imaging time per mouse is 40 minutes using a multiple-mouse MRI scanner (Varian, Palo Alto, CA) that can image four mice at once to increase our throughput. The mice are imaged with a T1-weighted spin echo sequence to highlight contrast from a dose of MnCl2 (20 mg/kg) injected intraperitoneally 48 hours before imaging.

We are testing our screening method in mice that are homozygous for the cerebellar deficient folia (cdf) mutation (The Jackson Laboratory, Bar Harbor, ME), which causes abnormal morphology in the cerebellum and hippocampus, and disrupts fear conditioning and prepulse inhibition of the startle response.

Currently, six normal mice (three wildtype and three heterozygotes) and one mutant mouse at 11 weeks of age have been imaged. We created an average brain image of the normal mice by non-linearly registering the individual images into an unbiased, common co-ordinate space. We then compared the image of the mutant brain to that average image and identified the expected changes in morphology in the cerebellum and hippocampus, as well as changes in ventricular morphology. As more mice are imaged, we will be able to make a statistically significant comparison between the wildtype and cdf/cdf mutant brain morphology using shape and size metrics.

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