Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy
| العنوان: | Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy |
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| المؤلفون: | Cyrille Vaillend, Amel Saoudi, Catherine Sebrié, Aurélie Goyenvalle, Faouzi Zarrouki, Charlotte Izabelle |
| المساهمون: | Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité BioMaps (BIOMAPS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Disease Models & Mechanisms Disease Models & Mechanisms, 2021, 14 (9), pp.dmm049028. ⟨10.1242/dmm.049028⟩ Disease Models & Mechanisms, Cambridge Company of Biologists, 2021, 14 (9), pp.dmm049028. ⟨10.1242/dmm.049028⟩ Disease Models & Mechanisms, Vol 14, Iss 9 (2021) article-version (VoR) Version of Record |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | musculoskeletal diseases, Duchenne muscular dystrophy, Neuromuscular Disease Models, congenital, hereditary, and neonatal diseases and abnormalities, Neuroscience (miscellaneous), Intellectual disability, Medicine (miscellaneous), Fear conditioning, Anxiety, General Biochemistry, Genetics and Molecular Biology, Dystrophin, Mice, Exon, Immunology and Microbiology (miscellaneous), In vivo, Pathology, medicine, Animals, Humans, RB1-214, Brain dystrophins, medicine.diagnostic_test, business.industry, Brain, Magnetic resonance imaging, Exons, medicine.disease, Muscular Dystrophy, Duchenne, Disease Models, Animal, Mice, Inbred mdx, Medicine, Emotional behavior, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], DMD mouse model, medicine.symptom, business, Neuroscience, Research Article |
| الوصف: | The exon-52-deleted mdx52 mouse is a critical model of Duchenne muscular dystrophy (DMD), as it features a deletion in a hotspot region of the DMD gene, frequently mutated in patients. Deletion of exon 52 impedes expression of several brain dystrophins (Dp427, Dp260 and Dp140), thus providing a key model for studying the cognitive impairment associated with DMD and testing rescuing strategies. Here, using in vivo magnetic resonance imaging and neurohistology, we found no gross brain abnormalities in mdx52 mice, suggesting that the neural dysfunctions in this model are likely at the level of brain cellular functionalities. Then, we investigated emotional behavior and fear learning performance of mdx52 mice compared to mdx mice that only lack Dp427 to focus on behavioral phenotypes that could be used in future comparative preclinical studies. mdx52 mice displayed enhanced anxiety and a severe impairment in learning an amygdala-dependent Pavlovian association. These replicable behavioral outcome measures are reminiscent of the internalizing problems reported in a quarter of DMD patients, and will be useful for preclinical estimation of the efficacy of treatments targeting brain dysfunctions in DMD. Summary: The mdx52 mouse model of Duchenne muscular dystrophy lacks brain Dp427 and Dp140 dystrophins, and exhibits emotional, behavioral and learning phenotypes that are relevant for use in preclinical studies of the disorder. |
| اللغة: | English |
| تدمد: | 1754-8403 1754-8411 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08d925b2f297a821e724b3b33ad4221e https://hal.science/hal-03407894/document |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....08d925b2f297a821e724b3b33ad4221e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17548403 17548411 |
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