Abstract #1226

Vcan mutation leads to sex-specific changes in white matter microstructure in mice

Cristiana Tisca¹, Mohamed Tachrount ¹, Frederik Lange¹, Chaoyue Wang¹, Lily Qiu¹, Javier Barallobre-Barreiro², Marika Fava², Manuel Mayr², Jason Lerch^1,3,4, Aurea Martins-Bach¹, and Karla Miller¹

¹Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom, ³Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, ⁴Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Recent genome-wide association studies using UK Biobank datasets have shown associations between diffusion-weighted MRI (dMRI) phenotypes and genetic loci associated with the human VCAN gene, spanning most white matter tracts. To understand the biological cause of this association, we acquired ex vivo structural and dMRI data in a Vcan mouse model and evaluated whether it displays similar changes in white matter microstructure. We show that male Vcan mice display related dMRI phenotypes to those associated with mutations in VCAN in humans. This gives us the ability to investigate the biological interpretations of human GWAS results using histology.

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