haploinsufficiency of cyfip1 produces fragile x-like phenotypes in micehaploinsufficiency cyfip1产生脆弱的像在小鼠表型.pdfVIP

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haploinsufficiency of cyfip1 produces fragile x-like phenotypes in micehaploinsufficiency cyfip1产生脆弱的像在小鼠表型.pdf

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haploinsufficiency of cyfip1 produces fragile x-like phenotypes in micehaploinsufficiency cyfip1产生脆弱的像在小鼠表型

Haploinsufficiency of Cyfip1 Produces Fragile X-Like Phenotypes in Mice Ozlem Bozdagi1,2., Takeshi Sakurai1,2.¤a, Nathan Dorr1,2, Marion Pilorge 1,2¤b, Nagahide Takahashi 1,2¤c, Joseph D. Buxbaum1,2,3,4* 1 Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, United States of America, 3 Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, United States of America, 4 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America Abstract Background: Copy number variation (CNV) at the 15q11.2 region, which includes a gene that codes for CYFIP1 (cytoplasmic FMR1 interacting protein 1), has been implicated in autism, intellectual disability and additional neuropsychiatric phenotypes. In the current study we studied the function of Cyfip1 in synaptic physiology and behavior, using mice with a disruption of the Cyfip1 gene. Methodology/Principal Findings: We observed that in Cyfip1 heterozygous mice metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) induced by paired-pulse low frequency stimulation (PP-LFS) was significantly increased in comparison to wildtype mice. In addition, mGluR-LTD was not affected in the presence of protein synthesis inhibitor in the Cyfip1 heterozygous mice, while the same treatment inhibited LTD in wildtype littermate controls. mGluR-agonist (RS)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD was also significantly increased in hippocampal slices from Cyfip1 heterozygous mice and again showed independence