Abstract
Lack of expression of the fragile X mental retardation protein (FMRP), due to silencing of the FMR1 gene, causes the Fragile X syndrome. Although FMRP was characterized previously to be an RNA binding protein, little is known about its function or the mechanisms underlying the Fragile X syndrome. Here we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit, GluR1, was decreased in the cortical synapses, but not in the hippocampus or cerebellum, of FMR1 gene knockout mice. Reduced long-term potentiation (LTP) was also found in the cortex but not in the hippocampus. Another RNA binding protein, FXR; the N-methyl-D-aspartate receptor subunit, NR2; and other learning-related proteins including c-fos, synapsin, myelin proteolipid protein, and cAMP response element binding protein were not different between FMR1 gene knockout and wild-type mice. These findings suggest that the depressed cortical GluR1 expression and LTP associated with FMRP deficiency could contribute to the Fragile X phenotype.
(C)2002 Elsevier Science (USA).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism*
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Cerebral Cortex / physiopathology
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Cyclic AMP Response Element-Binding Protein / metabolism
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Down-Regulation / genetics*
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics
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Fragile X Mental Retardation Protein
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Fragile X Syndrome / genetics
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Fragile X Syndrome / metabolism*
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Fragile X Syndrome / pathology
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Gene Expression Regulation / genetics
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Learning Disabilities / genetics
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Learning Disabilities / metabolism
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Learning Disabilities / physiopathology
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Liver / metabolism
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / genetics*
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Male
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Mice
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Mice, Knockout
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Myelin Proteolipid Protein / metabolism
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Myocardium / metabolism
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Nerve Tissue Proteins / deficiency*
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Nerve Tissue Proteins / genetics
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RNA-Binding Proteins / metabolism
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism*
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Receptors, N-Methyl-D-Aspartate / metabolism
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Synapses / drug effects
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Synapses / metabolism*
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Synapsins / metabolism
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Synaptic Membranes / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / genetics*
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Tetrodotoxin / pharmacology
Substances
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Cyclic AMP Response Element-Binding Protein
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Excitatory Amino Acid Antagonists
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FXR1 protein, human
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Fmr1 protein, mouse
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Myelin Proteolipid Protein
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NR2A NMDA receptor
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Nerve Tissue Proteins
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RNA-Binding Proteins
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Synapsins
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Fragile X Mental Retardation Protein
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Tetrodotoxin
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glutamate receptor ionotropic, AMPA 1