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Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome

Williams–Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS,...

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Autores principales: Giannoccaro, Silvia, Ferraguto, Celeste, Petroni, Valeria, Marcelly, Coline, Nogues, Xavier, Campuzano, Victoria, Pietropaolo, Susanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913557/
https://www.ncbi.nlm.nih.gov/pubmed/36766733
http://dx.doi.org/10.3390/cells12030391
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author Giannoccaro, Silvia
Ferraguto, Celeste
Petroni, Valeria
Marcelly, Coline
Nogues, Xavier
Campuzano, Victoria
Pietropaolo, Susanna
author_facet Giannoccaro, Silvia
Ferraguto, Celeste
Petroni, Valeria
Marcelly, Coline
Nogues, Xavier
Campuzano, Victoria
Pietropaolo, Susanna
author_sort Giannoccaro, Silvia
collection PubMed
description Williams–Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder.
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spelling pubmed-99135572023-02-11 Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome Giannoccaro, Silvia Ferraguto, Celeste Petroni, Valeria Marcelly, Coline Nogues, Xavier Campuzano, Victoria Pietropaolo, Susanna Cells Article Williams–Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder. MDPI 2023-01-21 /pmc/articles/PMC9913557/ /pubmed/36766733 http://dx.doi.org/10.3390/cells12030391 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Giannoccaro, Silvia
Ferraguto, Celeste
Petroni, Valeria
Marcelly, Coline
Nogues, Xavier
Campuzano, Victoria
Pietropaolo, Susanna
Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome
title Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome
title_full Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome
title_fullStr Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome
title_full_unstemmed Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome
title_short Early Neurobehavioral Characterization of the CD Mouse Model of Williams–Beuren Syndrome
title_sort early neurobehavioral characterization of the cd mouse model of williams–beuren syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913557/
https://www.ncbi.nlm.nih.gov/pubmed/36766733
http://dx.doi.org/10.3390/cells12030391
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