FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387485127> ?p ?o ?g. }

• W4387485127 abstract "Rearrangements within the AUTS2 region are associated with a rare syndromic disorder with intellectual disability, developmental delay and behavioral abnormalities as core features. In addition, smaller regional variants are linked to wide range of neuropsychiatric disorders, underscoring the gene's essential role in brain development. Like many essential neurodevelopmental genes, AUTS2 is large and complex, generating distinct long (AUTS2-l) and short (AUTS2-s) protein isoforms from alternative promoters. Although evidence suggests unique isoform functions, the contributions of each isoform to specific AUTS2-linked phenotypes have not been clearly resolved. Furthermore, Auts2 is widely expressed across the developing brain, but cell populations most central to disease presentation have not been determined. In this study, we focused on the specific roles of AUTS2-l in brain development, behavior, and postnatal brain gene expression, showing that brain-wide AUTS2-l ablation leads to specific subsets of the recessive pathologies associated with mutations in 3´ exons (exons 8-19) that disrupt both major isoforms. We identify downstream genes that could explain expressed phenotypes including hundreds of putative direct AUTS2-l target genes. Furthermore, in contrast to 3´ Auts2 mutations which lead to dominant hypoactivity, AUTS2-l loss-of-function is associated with dominant hyperactivity and repetitive behaviors, phenotypes exhibited by many human patients. Finally, we show that AUTS2-l ablation in Calbindin 1-expressing cell lineages is sufficient to yield learning/memory deficits and hyperactivity with abnormal dentate gyrus granule cell maturation, but not other phenotypic effects. These data provide new clues to in vivo AUTS2-l functions and novel information relevant to genotype-phenotype correlations in the human AUTS2 region." @default.
• W4387485127 created "2023-10-11" @default.
• W4387485127 creator A5056107539 @default.
• W4387485127 creator A5058151075 @default.
• W4387485127 creator A5067914271 @default.
• W4387485127 creator A5070132949 @default.
• W4387485127 creator A5074121951 @default.
• W4387485127 creator A5088873126 @default.
• W4387485127 date "2023-10-10" @default.
• W4387485127 modified "2023-10-12" @default.
• W4387485127 title "Isolated loss of the AUTS2 long isoform, brain-wide or targeted to <i>Calbindin</i>-lineage cells, generates a specific suite of brain, behavioral and molecular pathologies" @default.
• W4387485127 doi "https://doi.org/10.1093/genetics/iyad182" @default.
• W4387485127 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37816306" @default.
• W4387485127 hasPublicationYear "2023" @default.
• W4387485127 type Work @default.
• W4387485127 citedByCount "0" @default.
• W4387485127 crossrefType "journal-article" @default.
• W4387485127 hasAuthorship W4387485127A5056107539 @default.
• W4387485127 hasAuthorship W4387485127A5058151075 @default.
• W4387485127 hasAuthorship W4387485127A5067914271 @default.
• W4387485127 hasAuthorship W4387485127A5070132949 @default.
• W4387485127 hasAuthorship W4387485127A5074121951 @default.
• W4387485127 hasAuthorship W4387485127A5088873126 @default.
• W4387485127 hasConcept C104317684 @default.
• W4387485127 hasConcept C127716648 @default.
• W4387485127 hasConcept C148762608 @default.
• W4387485127 hasConcept C169760540 @default.
• W4387485127 hasConcept C2776464000 @default.
• W4387485127 hasConcept C36823959 @default.
• W4387485127 hasConcept C53345823 @default.
• W4387485127 hasConcept C54355233 @default.
• W4387485127 hasConcept C86803240 @default.
• W4387485127 hasConceptScore W4387485127C104317684 @default.
• W4387485127 hasConceptScore W4387485127C127716648 @default.
• W4387485127 hasConceptScore W4387485127C148762608 @default.
• W4387485127 hasConceptScore W4387485127C169760540 @default.
• W4387485127 hasConceptScore W4387485127C2776464000 @default.
• W4387485127 hasConceptScore W4387485127C36823959 @default.
• W4387485127 hasConceptScore W4387485127C53345823 @default.
• W4387485127 hasConceptScore W4387485127C54355233 @default.
• W4387485127 hasConceptScore W4387485127C86803240 @default.
• W4387485127 hasLocation W43874851271 @default.
• W4387485127 hasLocation W43874851272 @default.
• W4387485127 hasOpenAccess W4387485127 @default.
• W4387485127 hasPrimaryLocation W43874851271 @default.
• W4387485127 hasRelatedWork W1492410820 @default.
• W4387485127 hasRelatedWork W2013920666 @default.
• W4387485127 hasRelatedWork W2015757121 @default.
• W4387485127 hasRelatedWork W2042535624 @default.
• W4387485127 hasRelatedWork W2059640213 @default.
• W4387485127 hasRelatedWork W2077746656 @default.
• W4387485127 hasRelatedWork W2079739006 @default.
• W4387485127 hasRelatedWork W2365195844 @default.
• W4387485127 hasRelatedWork W2421860156 @default.
• W4387485127 hasRelatedWork W4385462331 @default.
• W4387485127 isParatext "false" @default.
• W4387485127 isRetracted "false" @default.
• W4387485127 workType "article" @default.