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Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior
Adhesion molecules play major roles in cell proliferation, migration, survival, neurite outgrowth and synapse formation during nervous system development and in adulthood. The neural cell adhesion molecule L1 contributes to these functions during development and in synapse formation and synaptic pla...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216033/ https://www.ncbi.nlm.nih.gov/pubmed/37238646 http://dx.doi.org/10.3390/biom13050776 |
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author | Congiu, Ludovica Granato, Viviana Jakovcevski, Igor Kleene, Ralf Fernandes, Luciana Freitag, Sandra Kneussel, Matthias Schachner, Melitta Loers, Gabriele |
author_facet | Congiu, Ludovica Granato, Viviana Jakovcevski, Igor Kleene, Ralf Fernandes, Luciana Freitag, Sandra Kneussel, Matthias Schachner, Melitta Loers, Gabriele |
author_sort | Congiu, Ludovica |
collection | PubMed |
description | Adhesion molecules play major roles in cell proliferation, migration, survival, neurite outgrowth and synapse formation during nervous system development and in adulthood. The neural cell adhesion molecule L1 contributes to these functions during development and in synapse formation and synaptic plasticity after trauma in adulthood. Mutations of L1 in humans result in L1 syndrome, which is associated with mild-to-severe brain malformations and mental disabilities. Furthermore, mutations in the extracellular domain were shown to cause a severe phenotype more often than mutations in the intracellular domain. To explore the outcome of a mutation in the extracellular domain, we generated mice with disruption of the dibasic sequences RK and KR that localize to position (858)RKHSKR(863) in the third fibronectin type III domain of murine L1. These mice exhibit alterations in exploratory behavior and enhanced marble burying activity. Mutant mice display higher numbers of caspase 3-positive neurons, a reduced number of principle neurons in the hippocampus, and an enhanced number of glial cells. Experiments suggest that disruption of the dibasic sequence in L1 results in subtle impairments in brain structure and functions leading to obsessive-like behavior in males and reduced anxiety in females. |
format | Online Article Text |
id | pubmed-10216033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102160332023-05-27 Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior Congiu, Ludovica Granato, Viviana Jakovcevski, Igor Kleene, Ralf Fernandes, Luciana Freitag, Sandra Kneussel, Matthias Schachner, Melitta Loers, Gabriele Biomolecules Article Adhesion molecules play major roles in cell proliferation, migration, survival, neurite outgrowth and synapse formation during nervous system development and in adulthood. The neural cell adhesion molecule L1 contributes to these functions during development and in synapse formation and synaptic plasticity after trauma in adulthood. Mutations of L1 in humans result in L1 syndrome, which is associated with mild-to-severe brain malformations and mental disabilities. Furthermore, mutations in the extracellular domain were shown to cause a severe phenotype more often than mutations in the intracellular domain. To explore the outcome of a mutation in the extracellular domain, we generated mice with disruption of the dibasic sequences RK and KR that localize to position (858)RKHSKR(863) in the third fibronectin type III domain of murine L1. These mice exhibit alterations in exploratory behavior and enhanced marble burying activity. Mutant mice display higher numbers of caspase 3-positive neurons, a reduced number of principle neurons in the hippocampus, and an enhanced number of glial cells. Experiments suggest that disruption of the dibasic sequence in L1 results in subtle impairments in brain structure and functions leading to obsessive-like behavior in males and reduced anxiety in females. MDPI 2023-04-29 /pmc/articles/PMC10216033/ /pubmed/37238646 http://dx.doi.org/10.3390/biom13050776 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 Congiu, Ludovica Granato, Viviana Jakovcevski, Igor Kleene, Ralf Fernandes, Luciana Freitag, Sandra Kneussel, Matthias Schachner, Melitta Loers, Gabriele Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior |
title | Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior |
title_full | Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior |
title_fullStr | Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior |
title_full_unstemmed | Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior |
title_short | Mice Mutated in the Third Fibronectin Domain of L1 Show Enhanced Hippocampal Neuronal Cell Death, Astrogliosis and Alterations in Behavior |
title_sort | mice mutated in the third fibronectin domain of l1 show enhanced hippocampal neuronal cell death, astrogliosis and alterations in behavior |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216033/ https://www.ncbi.nlm.nih.gov/pubmed/37238646 http://dx.doi.org/10.3390/biom13050776 |
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