CPEB1 depletion ameliorates fragile X syndrome

Posted by & filed under Part 05: CHROMOSOMES.

Fragile X syndrome (FXS) is caused by transcriptional silencing of FMR1 encoding the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element–binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. The authors of this study found that Fmr1 -/y Cpeb1 -/- double-knockout mice show amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1 -/y mice rescued working memory deficits, demonstrating reversal of this FXS phenotype. Results of this study suggest that disruption of translational homeostasis is causal for FXS and maintenance of this homeostasis by FMRP and CPEB1 is required for normal neurologic function.


Posted by Nicola Brunetti-Pierri, MD, FACMG

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