tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mousetensor-based形态测量学和体视学揭示大脑病理学complexin1敲除老鼠.pdf

Tensor-Based Morphometry and Stereology Reveal Brain Pathology in the Complexin1 Knockout Mouse 1 2,3 1 1 Catherine Kielar , Stephen J. Sawiak , Paloma Navarro Negredo , Desmond H. Y. Tse , A. Jennifer Morton1* 1 Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom, 2 Wolfson Brain Imaging Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom, 3 Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom Abstract Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx12/ 2) have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx12/ 2 mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx12/ 2 mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx12/ 2 and Cplx1+/+ mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx12/ 2 mice when compared to Cplx1+/+ animals. Our study is the first to describe pathological changes in Cplx12/ 2 mouse brain. We suggest that the ataxia in Cplx12/ 2 mice is likely to be due to pathologica