The X-Linked Intellectual Disability Gene, ZDHHC9 , Is Important for Oligodendrocyte Subtype Determination and Myelination.

ABSTRACT: Two percent of patients with X-linked intellectual disability (XLID) exhibit loss-of-function mutations in the enzyme, ZDHHC9. One of the main anatomical deficits observed in these patients is a decrease in corpus callosum volume and a concurrent disruption in white matter integrity. In this study, we demonstrate that deletion of Zdhhc9 in mice disrupts the balance of mature oligodendrocyte subtypes within the corpus callosum. While overall mature oligodendrocyte numbers are unchanged, there is a marked increase in MOL5/6 cells that are enriched in genes associated with cell adhesion and synapses, and a concomitant decrease in MOL2/3 cells that are enriched in genes associated with myelination. In line with this, we observed a decrease in the density of myelinated axons and disruptions in

SUBMITTER: White RB 

PROVIDER: S-EPMC12121472 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature