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Title: | Deregulated transcription and proteostasis in adult mapt knockout mouse |
Author: | Andrés Benito, Pol Flores de los Heros, África Busquet-Areny, Sara Carmona Murillo, Margarita Ausín, Karina Cartas Cejudo, Paz Lachén Montes, Mercedes Río Fernández, José Antonio del Fernández Irigoyen, Joaquín Santamaría, Enrique Ferrer, Isidro (Ferrer Abizanda) |
Keywords: | Escorça cerebral Ratolins (Animals de laboratori) Teixit nerviós Neurones Cerebral cortex Mice (Laboratory animals) Nerve tissue Neurons |
Issue Date: | 31-Mar-2023 |
Publisher: | MDPI |
Abstract: | Transcriptomics 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, β-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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms24076559 |
It is part of: | International Journal of Molecular Sciences, 2023, vol. 24, num. 7, p. 6559 |
URI: | http://hdl.handle.net/2445/198569 |
Related resource: | https://doi.org/10.3390/ijms24076559 |
ISSN: | 1661-6596 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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