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PMID: 12032354 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Altered synaptic plasticity in a mouse model of fragile X mental retardation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 11 ·2002-05-28 ·Pages 7746-50

Huber KM, Gallagher SM, Warren ST, Bear MF

Abstract

Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.

MeSH Terms
Animals Disease Models, Animal Fragile X Mental Retardation Protein Fragile X Syndrome/genetics,physiopathology Humans Intellectual Disability/genetics,physiopathology Mice Mice, Knockout Models, Neurological Mutation Nerve Tissue Proteins/genetics Neuronal Plasticity/physiology Protein Biosynthesis RNA, Messenger/genetics RNA-Binding Proteins Synapses/physiology Transcription, Genetic
Chemicals
FMR1 protein, human Fmr1 protein, mouse Nerve Tissue Proteins RNA, Messenger RNA-Binding Proteins Fragile X Mental Retardation Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Huber Kimberly M
Department of Neuroscience, Howard Hughes Medical Institute, Brown University, Providence, RI 02912, USA.
Gallagher Sean M
Warren Stephen T
Bear Mark F
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.122205699
Published
2002-05-28
Pages
7746-50
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC124340
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.122205699 PMC Full Text View journal details
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