| http://purl.uniprot.org/citations/31600777 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31600777 | http://www.w3.org/2000/01/rdf-schema#comment | "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's 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+/-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."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddz233"xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Wang W."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Yin J."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Lewis R.A."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Chen C.A."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Schaaf C.P."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Wu S.M."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Xia A."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Lopez J."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Zoghbi H.Y."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Pedersen S.E."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Raman A."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Pautler R.G."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Pereira F.A."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Ruiz F.R."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Rech M.E."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "Seymour M.L."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/author | "van der Heijden M.E."xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/31600777 | http://purl.uniprot.org/core/pages | "705-715"xsd:string |