Mutations in USP9X are associated with X-linked intellectual disability and disrupt neuronal cell migration and growth.

ABSTRACT: With a wealth of disease-associated DNA variants being recently reported, the challenges of providing their functional characterization are mounting. Previously, as part of a large systematic resequencing of the X chromosome in 208 unrelated families with nonsyndromic X-linked intellectual disability, we identified three unique variants (two missense and one protein truncating) in USP9X. To assess the functional significance of these variants, we took advantage of the Usp9x knockout mouse we generated. Loss of Usp9x causes reduction in both axonal growth and neuronal cell migration. Although overexpression of wild-type human USP9X rescued these defects, all three USP9X variants failed to rescue axonal growth, caused reduced USP9X protein localization in axonal growth cones, and (in 2/3 var

SUBMITTER: Homan CC 

PROVIDER: S-EPMC3951929 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature