دورية أكاديمية
أعرض في EDS

Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats.

التفاصيل البيبلوغرافية
العنوان: Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats.
المؤلفون: Golden CEM; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Breen MS; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Koro L; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Sonar S; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Niblo K; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Browne A; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Burlant N; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Di Marino D; Faculty of Biomedical Sciences, Institute of Computational Science, Center for Computational Medicine in Cardiology, Università della Svizzera Italiana (USI), Lugano, Switzerland.; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy., De Rubeis S; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Baxter MG; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Buxbaum JD; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Harony-Nicolas H; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
المصدر: Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2019 May 01; Vol. 29 (5), pp. 2228-2244.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 9110718 Publication Model: Print Cited Medium: Internet ISSN: 1460-2199 (Electronic) Linking ISSN: 10473211 NLM ISO Abbreviation: Cereb Cortex Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Oxford University Press, c1991-
مواضيع طبية MeSH: Gene Expression Regulation*, Attention Deficit Disorder with Hyperactivity/*genetics , Attention Deficit Disorder with Hyperactivity/*metabolism , Fragile X Mental Retardation Protein/*metabolism , Fragile X Syndrome/*genetics , Fragile X Syndrome/*metabolism , Prefrontal Cortex/*metabolism, Animals ; Attention/physiology ; Disease Models, Animal ; Female ; Fragile X Mental Retardation Protein/genetics ; Gene Regulatory Networks ; Male ; Rats, Sprague-Dawley ; Rats, Transgenic
مستخلص: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene. It is a leading monogenic cause of autism spectrum disorder and inherited intellectual disability and is often comorbid with attention deficits. Most FXS cases are due to an expansion of CGG repeats leading to suppressed expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA metabolism. We found that the previously published Fmr1 knockout rat model of FXS expresses an Fmr1 transcript with an in-frame deletion of exon 8, which encodes for the K-homology (KH) RNA-binding domain, KH1. Notably, 3 pathogenic missense mutations associated with FXS lie in the KH domains. We observed that the deletion of exon 8 in rats leads to attention deficits and to alterations in transcriptional profiles within the medial prefrontal cortex (mPFC), which map to 2 weighted gene coexpression network modules. These modules are conserved in human frontal cortex and enriched for known FMRP targets. Hub genes in these modules represent potential therapeutic targets for FXS. Taken together, these findings indicate that attentional testing might be a reliable cross-species tool for investigating FXS and identify dysregulated conserved gene networks in a relevant brain region.
(© The Author(s) 2019. Published by Oxford University Press.)
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معلومات مُعتمدة: F31 MH115656 United States MH NIMH NIH HHS; R01 MH101584 United States MH NIMH NIH HHS
فهرسة مساهمة: Keywords: 5-choice serial reaction time task; RNA sequencing; fragile X syndrome; medial prefrontal cortex
المشرفين على المادة: 0 (Fmr1 protein, rat)
139135-51-6 (Fragile X Mental Retardation Protein)
تواريخ الأحداث: Date Created: 20190317 Date Completed: 20200617 Latest Revision: 20200617
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC6458915
DOI: 10.1093/cercor/bhz029
PMID: 30877790
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2199
DOI:10.1093/cercor/bhz029