FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3109792347> ?p ?o ?g. }

• W3109792347 abstract "Abstract Background The regulation of protein synthesis is a critical step in gene expression, and its dysfunction is implicated in autism spectrum disorder (ASD). The eIF4E homologous protein (4EHP, also termed eIF4E2) binds to the mRNA 5′ cap to repress translation. The stability of 4EHP is maintained through physical interaction with GRB10 interacting GYF protein 2 (GIGYF2). Gene-disruptive mutations in GIGYF2 are linked to ASD, but causality is lacking. We hypothesized that GIGYF2 mutations cause ASD by disrupting 4EHP function. Methods Since homozygous deletion of either gene is lethal, we generated a cell-type-specific knockout model where Eif4e2 (the gene encoding 4EHP) is deleted in excitatory neurons of the forebrain (4EHP-eKO). In this model, we investigated ASD-associated synaptic plasticity dysfunction, ASD-like behaviors, and global translational control. We also utilized mice lacking one copy of Gigyf2 , Eif4e2 or co-deletion of one copy of each gene to further investigate ASD-like behaviors. Results 4EHP is expressed in excitatory neurons and synaptosomes, and its amount increases during development. 4EHP-eKO mice display exaggerated mGluR-LTD, a phenotype frequently observed in mouse models of ASD. Consistent with synaptic plasticity dysfunction, the mice displayed social behavior impairments without being confounded by deficits in olfaction, anxiety, locomotion, or motor ability. Repetitive behaviors and vocal communication were not affected by loss of 4EHP in excitatory neurons. Heterozygous deletion of either Gigyf2 , Eif4e2 , or both genes in mice did not result in ASD-like behaviors (i.e. decreases in social behavior or increases in marble burying). Interestingly, exaggerated mGluR-LTD and impaired social behaviors were not attributed to changes in hippocampal global protein synthesis, which suggests that 4EHP and GIGYF2 regulate the translation of specific mRNAs to mediate these effects. Limitations This study did not identify which genes are translationally regulated by 4EHP and GIGYF2. Identification of mistranslated genes in 4EHP-eKO mice might provide a mechanistic explanation for the observed impairment in social behavior and exaggerated LTD. Future experiments employing affinity purification of translating ribosomes and mRNA sequencing in 4EHP-eKO mice will address this relevant issue. Conclusions Together these results demonstrate an important role of 4EHP in regulating hippocampal plasticity and ASD-associated social behaviors, consistent with the link between mutations in GIGYF2 and ASD." @default.
• W3109792347 created "2020-12-07" @default.
• W3109792347 creator A5002603479 @default.
• W3109792347 creator A5018003707 @default.
• W3109792347 creator A5019957951 @default.
• W3109792347 creator A5024025818 @default.
• W3109792347 creator A5035302108 @default.
• W3109792347 creator A5046176525 @default.
• W3109792347 creator A5069167592 @default.
• W3109792347 date "2020-11-23" @default.
• W3109792347 modified "2023-10-16" @default.
• W3109792347 title "The eIF4E homolog 4EHP (eIF4E2) regulates hippocampal long-term depression and impacts social behavior" @default.
• W3109792347 cites W1520611165 @default.
• W3109792347 cites W1534107680 @default.
• W3109792347 cites W1546528060 @default.
• W3109792347 cites W1798244663 @default.
• W3109792347 cites W1851485572 @default.
• W3109792347 cites W1894591827 @default.
• W3109792347 cites W1964160578 @default.
• W3109792347 cites W1965456948 @default.
• W3109792347 cites W1992299484 @default.
• W3109792347 cites W2008627757 @default.
• W3109792347 cites W2008718844 @default.
• W3109792347 cites W2011463948 @default.
• W3109792347 cites W2018660905 @default.
• W3109792347 cites W2022415974 @default.
• W3109792347 cites W2031785254 @default.
• W3109792347 cites W2042892138 @default.
• W3109792347 cites W2048862315 @default.
• W3109792347 cites W2058852389 @default.
• W3109792347 cites W2062737903 @default.
• W3109792347 cites W2070801122 @default.
• W3109792347 cites W2079838847 @default.
• W3109792347 cites W2083730253 @default.
• W3109792347 cites W2085604313 @default.
• W3109792347 cites W2097231159 @default.
• W3109792347 cites W2108994842 @default.
• W3109792347 cites W2113526568 @default.
• W3109792347 cites W2116276594 @default.
• W3109792347 cites W2121879383 @default.
• W3109792347 cites W2132802598 @default.
• W3109792347 cites W2133659563 @default.
• W3109792347 cites W2146702633 @default.
• W3109792347 cites W2154761542 @default.
• W3109792347 cites W2157742595 @default.
• W3109792347 cites W2162423225 @default.
• W3109792347 cites W2171632740 @default.
• W3109792347 cites W2263774645 @default.
• W3109792347 cites W2427010553 @default.
• W3109792347 cites W2524440579 @default.
• W3109792347 cites W2553463105 @default.
• W3109792347 cites W2606068329 @default.
• W3109792347 cites W2613992235 @default.
• W3109792347 cites W2615129326 @default.
• W3109792347 cites W2626605337 @default.
• W3109792347 cites W2734527849 @default.
• W3109792347 cites W2735357942 @default.
• W3109792347 cites W2767324723 @default.
• W3109792347 cites W2787697704 @default.
• W3109792347 cites W2887287746 @default.
• W3109792347 cites W2898096243 @default.
• W3109792347 cites W2898813564 @default.
• W3109792347 cites W2903631495 @default.
• W3109792347 cites W2952743173 @default.
• W3109792347 cites W2969788462 @default.
• W3109792347 cites W2972591097 @default.
• W3109792347 cites W3035013740 @default.
• W3109792347 cites W4210708461 @default.
• W3109792347 cites W852219955 @default.
• W3109792347 doi "https://doi.org/10.1186/s13229-020-00394-7" @default.
• W3109792347 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7682028" @default.
• W3109792347 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33225984" @default.
• W3109792347 hasPublicationYear "2020" @default.
• W3109792347 type Work @default.
• W3109792347 sameAs 3109792347 @default.
• W3109792347 citedByCount "7" @default.
• W3109792347 countsByYear W31097923472021 @default.
• W3109792347 countsByYear W31097923472022 @default.
• W3109792347 countsByYear W31097923472023 @default.
• W3109792347 crossrefType "journal-article" @default.
• W3109792347 hasAuthorship W3109792347A5002603479 @default.
• W3109792347 hasAuthorship W3109792347A5018003707 @default.
• W3109792347 hasAuthorship W3109792347A5019957951 @default.
• W3109792347 hasAuthorship W3109792347A5024025818 @default.
• W3109792347 hasAuthorship W3109792347A5035302108 @default.
• W3109792347 hasAuthorship W3109792347A5046176525 @default.
• W3109792347 hasAuthorship W3109792347A5069167592 @default.
• W3109792347 hasBestOaLocation W31097923471 @default.
• W3109792347 hasConcept C104317684 @default.
• W3109792347 hasConcept C112592302 @default.
• W3109792347 hasConcept C118552586 @default.
• W3109792347 hasConcept C15744967 @default.
• W3109792347 hasConcept C169760540 @default.
• W3109792347 hasConcept C170493617 @default.
• W3109792347 hasConcept C182704531 @default.
• W3109792347 hasConcept C205778803 @default.
• W3109792347 hasConcept C2778538070 @default.
• W3109792347 hasConcept C2779715522 @default.
• W3109792347 hasConcept C529278444 @default.
• W3109792347 hasConcept C54355233 @default.

• next