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Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility

Dos Santos Silva, Ana, Haddon, Josephine, Syed, Yasir Ahmed, Trent, Simon, Tzu-Ching, E.Lin, Patel, Yateen, Carter, Jenny, Haan, Niels, Honey, Robert, Humby, Trevor, Assaf, Yaniv, Owen, Michael, Linden, David, Hall, Jeremy and Wilkinson, Lawrence 2019. Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility. Nature 10 , -. 10.1038/s41467-019-11119-7

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Abstract

The biological basis of the increased risk for psychiatric disorders seen in 15q11.2 copy number deletion is unknown. Previous work has shown disturbances in white matter tracts in human carriers of the deletion. Here, in a novel rat model, we recapitulated low dosage of the candidate risk gene CYFIP1 present within the 15q11.2 interval. Using diffusion tensor imaging, we first showed extensive white matter changes in Cyfip1 mutant rats, which were most pronounced in the corpus callosum and external capsule. Transmission electron microscopy showed that these changes were associated with thinning of the myelin sheath in the corpus callosum. Myelin thinning was independent of changes in axon number or diameter but was associated with effects on mature oligodendrocytes, including aberrant intracellular distribution of myelin basic protein. Finally, we demonstrated effects on cognitive phenotypes sensitive to both disruptions in myelin and callosal circuitry.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Biosciences
Medicine
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Nature Publishing Group
ISSN: 0028-0836
Funders: Wellcome Trust
Date of First Compliant Deposit: 27 June 2019
Date of Acceptance: 20 June 2019
Last Modified: 14 Aug 2019 08:45
URI: http://orca.cf.ac.uk/id/eprint/123764

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