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Series GSE40852 Query DataSets for GSE40852
Status Public on Jan 01, 2015
Title Overexpression of disease-associated CYFIP1 alters cellular and synaptic morphology through mTOR dysregulation of mTOR signaling
Organism Mus musculus
Experiment type Expression profiling by array
Summary Rare genomic gains at 15q11-q13 are observed in 1-2% of individuals with an Autism Spectrum Disorder (ASD). Because many genes are included here and breakpoints vary between cases, the potential contribution of specific genes is unclear. Cytoplasmic FMR1 interacting protein 1 (CYFIP1) is interesting in this regard given the association of smaller overlapping deletions with each of schizophrenia and intellectual disability. Towards an understanding of how increased CYFIP1 dosage might predispose to neurodevelopmental disease we investigated the consequence of overexpression in multiple systems. We show that CYFIP1 mRNA is increased in lymphoblastoid cells and human brain as a function of 15q dosage. Towards mechanisms, we determined that overexpression of CYFIP1 results in cellular abnormalities in SY5Y cells and mouse neuronal progenitors. Identical abnormalities, as well as anomalies in synaptic morphology, were seen after comparing two BAC transgenic strains to controls. Gene expression profiling at embryonic day 15 identified genes differentially expressed between transgenic and control mice and highlighted dysregulation of mTOR signaling. Finally, treatment of mouse neuronal progenitors with an mTOR inhibitor (Rapamycin) rescued morphologic abnormalities resulting from CYFIP1 overexpression. Together, these data are consistent with the notion that normalization of mTOR signaling, emerging as an important point of convergence in the ASDs, may be of clinical utility in genetically selected populations with a variety of neurodevelopmental disorders.
Overall design Mice harboring a Cyfip1 spanning BAC clone (RP24-333C15) were generated in the UCLA transgenic core ( by injection into C57BL/6J pronuclei. Transgenic mice were identified by PCR screening of tail derived DNA.
Contributor(s) Oguro-Ando A, Rosensweig C, Herman E, Nishimura Y, Werling D, Bill B, Berg J, Gao F, Coppola G, Abrahams B, Geschwind D
Citation(s) 25311365
Submission date Sep 13, 2012
Last update date Jun 14, 2018
Contact name Giovanni Coppola
Phone 310-794-4172
Organization name UCLA
Department Psychiatry and Neurology
Lab Neurogenetics
Street address 1524 Gonda, 695 Charles Young Drive South
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (6)
GSM1003283 DW91.2_Tg_M
GSM1003284 DW301_WT_M
GSM1003285 DW292_Tg_M
BioProject PRJNA175113

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Supplementary file Size Download File type/resource
GSE40852_RAW.tar 3.1 Mb (http)(custom) TAR
GSE40852_matrix_non-normalized_data.txt.gz 726.7 Kb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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