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Automated Behavioral Phenotyping Reveals Presymptomatic Alterations in a SCA3 Genetrap Mouse Model

Journal of Genetics and Genomics 2012年第6期39卷 287-299页

作者： Jeannette Hübener Nicolas Casadei peter teismann Mathias W. Seeliger Maria Bjrkqvist Stephan von Horsten Olaf Riess Huu Phuc Nguyen Department of Medical Genetics University of TubingenTubingen 72076Germany Institute of Medical Sciences University of AberdeenAB25 2ZDUK Division of Ocular Neurodegeneration Centre for OphthalmologyInstitute for Ophthalmic ResearchUniversity of TubingenTubingen 72076Germany Neuronal Survival Unit Department of Experimental Medical SciencesWallenberg Neuroscience CenterLund UniversityLund 221 84Sweden Experimental Therapy Franz-Penzoldt-CenterUniversity of Erlangen-NurnbergErlangen 91054Germany

Characterization of disease models of neurodegenerative disorders requires a systematic and comprehensive phenotyping in a highly standardized manner. Therefore, automated high-resolution behavior test systems such as the homecage based LabMaster system are of particular interest. We demonstrate the power of the automated LabMaster system by discovering previously unrecognized features of a recently characterized atxn3 mutant mouse model. This model provided neurological symptoms including gait ataxia, tremor, weight loss and premature death at the age of 12 months usually detectable just 2 weeks before the mice died. Moreover, using the LabMaster system we were able to detect hypoactivity in presymptomatic mutant mice in the dark as well as light phase. Additionally, we analyzed inflammation, immunological and hematological parameters, which indicated a reduced immune defense in phenotypic mice. Here we demonstrate that a detailed characterization even of organ systems that are usually not affected in SCA3 is important for further studies of pathogenesis and required for the preclinical therapeutic studies.

关键词： Automated homecage behavior Genetrap mouse model Spinocerebellar Ataxia Type 3

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