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Sex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specific Egr1 loss

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dc.contributor.authorSwilley, Codyen
dc.contributor.authorLin, Yuen
dc.contributor.authorZheng, Yuzeen
dc.contributor.authorXu, Xiguangen
dc.contributor.authorLiu, Minen
dc.contributor.authorJarome, Timothy J.en
dc.contributor.authorHodes, Georgia E.en
dc.contributor.authorXie, Hehuangen
dc.date.accessioned2024-01-22T17:44:30Zen
dc.date.available2024-01-22T17:44:30Zen
dc.date.issued2023-10-19en
dc.description.abstractThe transcription factor EGR1 is instrumental in numerous neurological processes, encompassing learning and memory as well as the reaction to stress. Egr1 complete knockout mice demonstrate decreased depressive or anxiety-like behavior and impaired performance in spatial learning and memory. Nevertheless, the specific functions of Egr1 in distinct cell types have been largely underexplored. In this study, we cataloged the behavioral and transcriptomic character of Nestin-Cre mediated Egr1 conditional knockout (Egr1cKO) mice together with their controls. Although the conditional knockout did not change nociceptive or anxiety responses, it triggered changes in female exploratory activity during anxiety testing. Hippocampus-dependent spatial learning in the object location task was unaffected, but female Egr1cKO mice did exhibit poorer retention during testing on a contextual fear conditioning task compared to males. RNA-seq data analyses revealed that the presence of the floxed Egr1 cassette or Nestin-Cre driver alone exerts a subtle influence on hippocampal gene expression. The sex-related differences were amplified in Nestin-Cre mediated Egr1 conditional knockout mice and female mice are more sensitive to the loss of Egr1 gene. Differentially expressed genes resulted from the loss of Egr1 in neuronal cell lineage were significantly associated with the regulation of Wnt signaling pathway, extracellular matrix, and axon guidance. Altogether, our results demonstrate that Nestin-Cre and the loss of Egr1 in neuronal cell lineage have distinct impacts on hippocampal gene expression in a sex-specific manner.en
dc.description.versionPublished versionen
dc.format.extent13 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 1240209 (Article number)en
dc.identifier.doihttps://doi.org/10.3389/fnins.2023.1240209en
dc.identifier.eissn1662-453Xen
dc.identifier.issn1662-4548en
dc.identifier.orcidHodes, Georgia [0000-0002-1551-2178]en
dc.identifier.otherPMC10623684en
dc.identifier.pmid37928724en
dc.identifier.urihttps://hdl.handle.net/10919/117546en
dc.identifier.volume17en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/37928724en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectsex differenceen
dc.subjectEgr1en
dc.subjectnestinen
dc.subjectRNA-seqen
dc.subjecthippocampusen
dc.subjectbehavioren
dc.titleSex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specific <i>Egr1</i> lossen
dc.title.serialFrontiers in Neuroscienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2023-10-03en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/School of Neuroscienceen

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