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Fluorescent transgenic mouse models for whole-brain imaging in health and disease

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dc.contributor.author Arias, Adrian
dc.contributor.author Manubens-Gil, Linus, 1989-
dc.contributor.author Dierssen, Mara
dc.date.accessioned 2023-01-18T07:35:03Z
dc.date.available 2023-01-18T07:35:03Z
dc.date.issued 2022
dc.identifier.citation Arias A, Manubens-Gil L, Dierssen M. Fluorescent transgenic mouse models for whole-brain imaging in health and disease. Front Mol Neurosci. 2022 Sep 23;15:958222. DOI: 10.3389/fnmol.2022.958222
dc.identifier.issn 1662-5099
dc.identifier.uri http://hdl.handle.net/10230/55324
dc.description.abstract A paradigm shift is occurring in neuroscience and in general in life sciences converting biomedical research from a descriptive discipline into a quantitative, predictive, actionable science. Living systems are becoming amenable to quantitative description, with profound consequences for our ability to predict biological phenomena. New experimental tools such as tissue clearing, whole-brain imaging, and genetic engineering technologies have opened the opportunity to embrace this new paradigm, allowing to extract anatomical features such as cell number, their full morphology, and even their structural connectivity. These tools will also allow the exploration of new features such as their geometrical arrangement, within and across brain regions. This would be especially important to better characterize brain function and pathological alterations in neurological, neurodevelopmental, and neurodegenerative disorders. New animal models for mapping fluorescent protein-expressing neurons and axon pathways in adult mice are key to this aim. As a result of both developments, relevant cell populations with endogenous fluorescence signals can be comprehensively and quantitatively mapped to whole-brain images acquired at submicron resolution. However, they present intrinsic limitations: weak fluorescent signals, unequal signal strength across the same cell type, lack of specificity of fluorescent labels, overlapping signals in cell types with dense labeling, or undetectable signal at distal parts of the neurons, among others. In this review, we discuss the recent advances in the development of fluorescent transgenic mouse models that overcome to some extent the technical and conceptual limitations and tradeoffs between different strategies. We also discuss the potential use of these strains for understanding disease.
dc.description.sponsorship The lab of MD was supported by the Departament d’Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya (Grups consolidats 2017 SGR 926, 2017 SGR 138). This research was funded by the Agencia Estatal de Investigación (PID2019-110755RB-I00/AEI/10.13039/501100011033), the European Union’s Horizon 2020 Research and Innovation Program under grant agreement No. 848077. This reflects only the author’s view, and the European Commission is not responsible for any use that may be made of the information it contains. Jerôme Lejeune Foundation (Grant Number 2002), NIH (Grant Number: 1R01EB 028159-01), Marató TV3 (#2016/20-30), and JPND (Heroes AC170006). The CRG acknowledges the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Program/Generalitat de Catalunya. The CIBER of Rare Diseases (CIBERER) is an initiative of the ISCIII.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Mol Neurosci. 2022 Sep 23;15:958222
dc.rights © 2022 Arias, Manubens-Gil and Dierssen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Fluorescent transgenic mouse models for whole-brain imaging in health and disease
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fnmol.2022.958222
dc.subject.keyword Cell detection and counting
dc.subject.keyword Computational neuroscience
dc.subject.keyword Fluorescent transgenic models
dc.subject.keyword Morphological reconstruction
dc.subject.keyword Whole-brain imaging
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848077
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110755RB-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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