Cyfip1 Haploinsufficient Rats Show White Matter Changes, Myelin Thinning, Abnormal Oligodendrocytes and Behavioural Inflexibility

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Aug 3

PMID 31371763

Citations 34

Authors

Ana I Silva

Josephine E Haddon

Yasir Ahmed Syed

Simon Trent

Tzu-Ching E Lin

Yateen Patel

Jenny Carter

Niels Haan

Robert C Honey

Trevor Humby

Yaniv Assaf

Michael J Owen

David E J Linden

Jeremy Hall

Lawrence S Wilkinson

Affiliations

Soon will be listed here.

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.

Citing Articles

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Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility.

Haddon J, Titherage D, Heckenast J, Carter J, Owen M, Hall J Transl Psychiatry. 2024; 14(1):256.

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