PMID:16055059

Citation	Koekkoek, SK, Yamaguchi, K, Milojkovic, BA, Dortland, BR, Ruigrok, TJ, Maex, R, De Graaf, W, Smit, AE, VanderWerf, F, Bakker, CE, Willemsen, R, Ikeda, T, Kakizawa, S, Onodera, K, Nelson, DL, Mientjes, E, Joosten, M, De Schutter, E, Oostra, BA, Ito, M and De Zeeuw, CI (2005) Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron 47:339-52
Abstract	Absence of functional FMRP causes Fragile X syndrome. Abnormalities in synaptic processes in the cerebral cortex and hippocampus contribute to cognitive deficits in Fragile X patients. So far, the potential roles of cerebellar deficits have not been investigated. Here, we demonstrate that both global and Purkinje cell-specific knockouts of Fmr1 show deficits in classical delay eye-blink conditioning in that the percentage of conditioned responses as well as their peak amplitude and peak velocity are reduced. Purkinje cells of these mice show elongated spines and enhanced LTD induction at the parallel fiber synapses that innervate these spines. Moreover, Fragile X patients display the same cerebellar deficits in eye-blink conditioning as the mutant mice. These data indicate that a lack of FMRP leads to cerebellar deficits at both the cellular and behavioral levels and raise the possibility that cerebellar dysfunctions can contribute to motor learning deficits in Fragile X patients.
Links	PubMed Online version:10.1016/j.neuron.2005.07.005
Keywords	Animals; Cerebellum/physiopathology; Conditioning, Eyelid; Dendrites/ultrastructure; Fragile X Mental Retardation Protein; Fragile X Syndrome/genetics; Fragile X Syndrome/pathology; Fragile X Syndrome/physiopathology; Gene Deletion; Humans; Long-Term Synaptic Depression; Male; Mice; Mice, Knockout; Mice, Mutant Strains; Models, Neurological; Nerve Fibers; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Purkinje Cells/metabolism; Purkinje Cells/ultrastructure; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Reflex, Startle
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:FMR1	involved_in	GO:1905244: regulation of modification of synaptic structure	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(CL:0000121)	Seeded From UniProt	complete

References

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