Deregulated transcription and proteostasis in adult mapt knockout mouse

Simple item page
dc.contributor.authorAndrés Benito, Pol
dc.contributor.authorFlores, África
dc.contributor.authorBusquet-Areny, Sara
dc.contributor.authorCarmona, Margarita
dc.contributor.authorAusín, Karina
dc.contributor.authorCartas Cejudo, Paz
dc.contributor.authorLachén Montes, Mercedes
dc.contributor.authorRío, José Antonio del
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorFerrer, Isidro
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2023-07-19T14:48:24Z
dc.date.available2023-07-19T14:48:24Z
dc.date.issued2023
dc.date.updated2023-07-19T14:31:35Z
dc.description.abstractTranscriptomics and phosphoproteomics were carried out in the cerebral cortex of B6.Cg-Mapttm1(EGFP)Klt (tau knockout: tau-KO) and wild-type (WT) 12 month-old mice to learn about the effects of tau ablation. Compared with WT mice, tau-KO mice displayed reduced anxiety-like behavior and lower fear expression induced by aversive conditioning, whereas recognition memory remained unaltered. Cortical transcriptomic analysis revealed 69 downregulated and 105 upregulated genes in tau-KO mice, corresponding to synaptic structures, neuron cytoskeleton and transport, and extracellular matrix components. RT-qPCR validated increased mRNA levels of col6a4, gabrq, gad1, grm5, grip2, map2, rab8a, tubb3, wnt16, and an absence of map1a in tau-KO mice compared with WT mice. A few proteins were assessed with Western blotting to compare mRNA expression with corresponding protein levels. Map1a mRNA and protein levels decreased. However, ¿-tubulin III and GAD1 protein levels were reduced in tau-KO mice. Cortical phosphoproteomics revealed 121 hypophosphorylated and 98 hyperphosphorylated proteins in tau-KO mice. Deregulated phosphoproteins were categorized into cytoskeletal (n = 45) and membrane proteins, including proteins of the synapses and vesicles, myelin proteins, and proteins linked to membrane transport and ion channels (n = 84), proteins related to DNA and RNA metabolism (n = 36), proteins connected to the ubiquitin-proteasome system (UPS) (n = 7), proteins with kinase or phosphatase activity (n = 21), and 22 other proteins related to variegated pathways such as metabolic pathways, growth factors, or mitochondrial function or structure. The present observations reveal a complex altered brain transcriptome and phosphoproteome in tau-KO mice with only mild behavioral alterations.en
dc.description.sponsorshipThe project leading to these results received funding from the “la Caixa” Foundation (ID 100010434) under the agreements LCF/PR/HR19/52160007, HR18-00452 to IF. We thank the CERCA Programme/Generalitat de Catalunya for institutional support. The Proteomics Platform of Navarrabiomed is a member of Proteored (PRB3-ISCIII), supported by grant PT17/0019/009 to J.F.-I. of the PE I + D + I 2013-2016 funded by ISCIII and FEDER. This work was funded by a grant from the Spanish Ministry of Science, Innovation, and Universities (Ref. PID2019-110356RB-I00) to J.F.-I. and E.S. and the Department of Economic and Business Development from the Government of Navarra (Ref. 0011-1411-2020-000028) to E.S.en
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.identifier.citationAndrés-Benito, P., Flores, Á., Busquet-Areny, S., Carmona, M., Ausín, K., Cartas-Cejudo, P., Lachén-Montes, M., Del Rio, J. A., Fernández-Irigoyen, J., Santamaría, E., Ferrer, I. (2023) Deregulated transcription and proteostasis in adult mapt knockout mouse. International Journal of Molecular Sciences, 24(7), 1-19. https://doi.org/10.3390/ijms24076559.en
dc.identifier.doi10.3390/ijms24076559
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/45803
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofInternational Journal of Molecular Sciences 2023, 24(7), 6559en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//0011-1411-2020-000028/
dc.relation.publisherversionhttps://doi.org/10.3390/ijms24076559
dc.rights2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCytoskeletonen
dc.subjectPhosphoproteomicsen
dc.subjectSynapseen
dc.subjectTau-KOen
dc.subjectTranscriptomicsen
dc.titleDeregulated transcription and proteostasis in adult mapt knockout mouseen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationda1d0e22-8279-4c6c-a7c5-cef564dc9542
relation.isAuthorOfPublicationcc02d7db-8e88-40d1-81e0-834617b4849d
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscoverycc02d7db-8e88-40d1-81e0-834617b4849d

Files

Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
Andres_DesregulatedTranscription.pdf
Size:
3.44 MB
Format:
Adobe Portable Document Format
Download
No Thumbnail Available
Name:
Andres_DesregulatedTranscription_MatCompl.zip
Size:
1.25 MB
Format:
ZIP
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.78 KB
Format:
Item-specific license agreed to upon submission
Description:
Download

Collections

Artículos de revista DCS - OZS Aldizkari artikuluak
Artículos de revista - Aldizkari artikuluak