Impaired cortical development and translational control in a missense mouse model of DDX3X syndrome.

ABSTRACT: Heterozygous mutations in the X-linked RNA helicase DDX3X cause DDX3X syndrome, a rare neurodevelopmental disorder associated with cortical malformations and autism spectrum disorder. Among ∼200 known DDX3X variants, half are missense, while the remainder are predicted loss-of-function (LoF) variants. LoF mouse models reveal that Ddx3x controls progenitors' ability to generate excitatory neurons. Yet, how missense mutations impact corticogenesis in vivo is unknown. Here, we generated a conditional mouse model of DDX3XT532M, a clinically severe and recurrent DDX3X syndrome variant found in affected females. Using Emx1-Cre-mediated expression of Ddx3xT532M in cortical progenitors, we showed that Ddx3xT532M alters corticogenesis. Ddx3xT532M conditional hemizygous males have severe microcephal

SUBMITTER: Poff AJ 

PROVIDER: S-EPMC12690540 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature