Cyfip1 haploinsufficiency is associated with white matter changes, myelin thinning, reduction of mature oligodendrocytes and behavioural inflexibility

Ana I. Silva, Josephine E. Haddon, Simon Trent, Yasir Ahmed Syed, Tzu-Ching E.Lin, Yateen Patel, Jenny Carter, Niels Haan, Rob C. Honey, Trevor Humby, Yaniv Assaf, David E. J. Linden, Michael J. Owen, Jeremy Hall, Lawrence S. Wilkinson

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Dec 11, 2018

Received Date: 23rd November 18

The biological basis of the increased risk for psychiatric disorders due to the pathogenic 15q11.2 copy number deletion is unknown. Previous work has shown disturbances in white matter tracts in human carriers of the deletion at this locus. Using a novel rat model, we have recapitulated low dosage of the candidate risk gene CYFIP1 present within the 15q11.2 interval to reveal alterations in white matter microstructure. Using diffusion tensor imaging, we first showed extensive white matter changes in Cyfip1 mutants that 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 a reduction in the number of mature oligodendrocytes. Finally, we demonstrated functional effects on cognitive phenotypes sensitive to both disruptions in myelin and callosal circuitry.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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Nature Communications

Nature Research, Springer Nature