Mouse behavioral mutants have neuroimaging abnormalities

Authors

  • Brian J. Nieman,

    1. Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
    3. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York
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  • Jason P. Lerch,

    1. Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada
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  • Nicholas A. Bock,

    1. Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
    3. Cerebral Microcirculation Unit/Laboratory of Functional and Molecular Imaging, NINDS/NIH, Bethesda, MD
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  • X. Josette Chen,

    1. Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
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  • John G. Sled,

    1. Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
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  • R. Mark Henkelman

    Corresponding author
    1. Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
    • Mouse Imaging Centre, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8
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Abstract

Impaired cognitive, memory, or motor performance is a distinguishing characteristic of neurological diseases. Although these symptoms are frequently the most evident in human patients, additional markers of disease are critical for proper diagnosis and staging. Noninvasive neuroimaging methods have become essential in this capacity and provide means of evaluating disease and tracking progression. These imaging methods are also becoming available to scientists in the research laboratory for assessment of animal models of neurological disease. Imaging in mouse models of neurological disease is of particular interest, owing to the availability of inbred strains and genetic manipulation tools that permit detailed investigation of the roles of various genes and gene products in disease pathogenesis. However, the relative prevalence of neuroimaging abnormalities in mice exhibiting neurological symptoms has not been reported. This prevalence has both theoretical and practical value because it is influenced by both the sensitivity of macroscopic anatomical measures to underlying genetic and disease processes and by the efficiency of neuroimaging in detecting and characterizing these effects. In this paper, we describe a meta-analysis of studies involving behavioral mouse mutants at our laboratory. In summary, we have evaluated 15 different mutant genotypes, of which 13 showed abnormal neuroimaging findings. This indicates a surprisingly high prevalence of neuroimaging abnormalities (87%) and suggests that disease processes affecting behavior generally alter neuroanatomy as well. As a consequence, neuroimaging provides a highly sensitive marker of neurological disease in mice exhibiting abnormal behavior. Hum Brain Mapp 2007. © 2007 Wiley-Liss, Inc.

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