We need your help! If you've ever found our data helpful, please take our impact survey (15 min). Your replies will help keep the data flowing to the scientific community. Please Click here for Survey

Unknown

Dataset Information

0

Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology.


ABSTRACT: Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes 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. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed 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. Finally, we find that FMRP and CPEB1 balance translation at the level of polypeptide elongation. Our results suggest that disruption of translational homeostasis is causal for FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary for normal neurologic function.

SUBMITTER: Udagawa T 

PROVIDER: S-EPMC3823751 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4313821 | BioStudies
2010-01-01 | S-EPMC2873207 | BioStudies
2011-01-01 | S-EPMC3433402 | BioStudies
1000-01-01 | S-EPMC4479623 | BioStudies
2016-01-01 | S-EPMC4999837 | BioStudies
2019-01-01 | S-EPMC6407369 | BioStudies
2014-01-01 | S-EPMC4287266 | BioStudies
2015-01-01 | S-EPMC4670233 | BioStudies
1000-01-01 | S-EPMC4355018 | BioStudies
2011-01-01 | S-EPMC3192166 | BioStudies