{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:53:50Z","timestamp":1790830430371,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","award":["9120"],"award-info":[{"award-number":["9120"]}],"id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007857","name":"Intellectual and Developmental Disabilities Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54HD083092"],"award-info":[{"award-number":["U54HD083092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) has been identified as an autosomal-dominant disorder characterized by a complex neurological phenotype, with high prevalence of intellectual disability and optic nerve atrophy\/hypoplasia. The syndrome is caused by loss-of-function mutations in NR2F1, which encodes a highly conserved nuclear receptor that serves as a transcriptional regulator. Previous investigations to understand the protein\u2019s role in neurodevelopment have mostly used mouse models with constitutive and tissue-specific homozygous knockout of Nr2f1. In order to represent the human disease more accurately, which is caused by heterozygous NR2F1 mutations, we investigated a heterozygous knockout mouse model and found that this model recapitulates some of the neurological phenotypes of BBSOAS, including altered learning\/memory, hearing defects, neonatal hypotonia and decreased hippocampal volume. The mice showed altered fear memory, and further electrophysiological investigation in hippocampal slices revealed significantly reduced long-term potentiation and long-term depression. These results suggest that a deficit or alteration in hippocampal synaptic plasticity may contribute to the intellectual disability frequently seen in BBSOAS. RNA-sequencing (RNA-Seq) analysis revealed significant differential gene expression in the adult Nr2f1+\/\u2212 hippocampus, including the up-regulation of multiple matrix metalloproteases, which are known to be critical for the development and the plasticity of the nervous system. Taken together, our studies highlight the important role of Nr2f1 in neurodevelopment. The discovery of impaired hippocampal synaptic plasticity in the heterozygous mouse model sheds light on the pathophysiology of altered memory and cognitive function in BBSOAS.<\/jats:p>","DOI":"10.1093\/hmg\/ddz233","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T19:24:29Z","timestamp":1569957869000},"page":"705-715","source":"Crossref","is-referenced-by-count":19,"title":["Nr2f1 heterozygous knockout mice recapitulate neurological phenotypes of Bosch-Boonstra-Schaaf optic atrophy syndrome and show impaired hippocampal synaptic plasticity"],"prefix":"10.1093","volume":"29","author":[{"given":"Chun-An","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX, 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M","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhandong","family":"Liu","sequence":"first","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, TX, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred A","family":"Pereira","sequence":"first","affiliation":[{"name":"Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robia G","family":"Pautler","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics-Cardiovascular Sciences 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J. Psychiatry"},{"key":"2020033009050323200_ref23","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1212\/WNL.56.7.972","article-title":"Amygdala and hippocampal volumes in children with down syndrome: a high-resolution MRI study","volume":"56","author":"Pinter","year":"2001","journal-title":"Neurology"},{"key":"2020033009050323200_ref24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1744-9081-3-54","article-title":"Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment","volume":"3","author":"Deboer","year":"2007","journal-title":"Behav. Brain Funct."},{"key":"2020033009050323200_ref25","first-page":"1629","article-title":"Gradient COUP-TFI expression is required for functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis","volume":"27","author":"Flore","year":"2017","journal-title":"Cereb. 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