Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring
Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3′-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-re...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1130055/full |
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| author | Elisabetta Golini Mara Rigamonti Marcello Raspa Ferdinando Scavizzi Germana Falcone Genevieve Gourdon Silvia Mandillo |
| author_facet | Elisabetta Golini Mara Rigamonti Marcello Raspa Ferdinando Scavizzi Germana Falcone Genevieve Gourdon Silvia Mandillo |
| author_sort | Elisabetta Golini |
| collection | DOAJ |
| description | Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3′-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-respiratory problems, hypersomnia, cognitive dysfunction and behavioral abnormalities. Sleep-related disturbances are among the most reported symptoms that negatively affect the quality of life of patients and that are present in early and adult-onset forms of the disease. DMSXL mice carry a mutated human DMPK transgene containing >1,000 CTGrepeats, modeling an early onset, severe form of DM1. They exhibit a pathologic neuromuscular phenotype and also synaptic dysfunction resulting in neurological and behavioral deficits similar to those observed in patients. Additionally, they are underweight with a very high mortality within the first month after birth presenting several welfare issues. To specifically explore sleep/rest-related behaviors of this frail DM1 mouse model we used an automated home cage-based system that allows 24/7 monitoring of their activity non-invasively. We tested male and female DMSXL mice and their wild-type (WT) littermates in Digital Ventilated Cages (DVCR) assessing activity and rest parameters on day and night for 5 weeks. We demonstrated that DMSXL mice show reduced activity and regularity disruption index (RDI), higher percentage of zero activity per each hour and longer periods of rest during the active phase compared to WT. This novel rest-related phenotype in DMSXL mice, assessed unobtrusively, could be valuable to further explore mechanisms and potential therapeutic interventions to alleviate the very common symptom of excessive daytime sleepiness in DM1 patients. |
| first_indexed | 2024-04-10T06:22:02Z |
| format | Article |
| id | doaj.art-cb5aa180ebb8459ebfc0f7d283fb6e4e |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-10T06:22:02Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-cb5aa180ebb8459ebfc0f7d283fb6e4e2023-03-02T04:30:05ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532023-03-011710.3389/fnbeh.2023.11300551130055Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoringElisabetta Golini0Mara Rigamonti1Marcello Raspa2Ferdinando Scavizzi3Germana Falcone4Genevieve Gourdon5Silvia Mandillo6Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo, ItalyTecniplast S.p.A., Buguggiate, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo, ItalyInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo, ItalySorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, Paris, FranceInstitute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo, ItalyMyotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3′-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-respiratory problems, hypersomnia, cognitive dysfunction and behavioral abnormalities. Sleep-related disturbances are among the most reported symptoms that negatively affect the quality of life of patients and that are present in early and adult-onset forms of the disease. DMSXL mice carry a mutated human DMPK transgene containing >1,000 CTGrepeats, modeling an early onset, severe form of DM1. They exhibit a pathologic neuromuscular phenotype and also synaptic dysfunction resulting in neurological and behavioral deficits similar to those observed in patients. Additionally, they are underweight with a very high mortality within the first month after birth presenting several welfare issues. To specifically explore sleep/rest-related behaviors of this frail DM1 mouse model we used an automated home cage-based system that allows 24/7 monitoring of their activity non-invasively. We tested male and female DMSXL mice and their wild-type (WT) littermates in Digital Ventilated Cages (DVCR) assessing activity and rest parameters on day and night for 5 weeks. We demonstrated that DMSXL mice show reduced activity and regularity disruption index (RDI), higher percentage of zero activity per each hour and longer periods of rest during the active phase compared to WT. This novel rest-related phenotype in DMSXL mice, assessed unobtrusively, could be valuable to further explore mechanisms and potential therapeutic interventions to alleviate the very common symptom of excessive daytime sleepiness in DM1 patients.https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1130055/fullDVC®DMSXLDM1digital biomarkersleepexcessive daytime sleepiness (EDS) |
| spellingShingle | Elisabetta Golini Mara Rigamonti Marcello Raspa Ferdinando Scavizzi Germana Falcone Genevieve Gourdon Silvia Mandillo Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring Frontiers in Behavioral Neuroscience DVC® DMSXL DM1 digital biomarker sleep excessive daytime sleepiness (EDS) |
| title | Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring |
| title_full | Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring |
| title_fullStr | Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring |
| title_full_unstemmed | Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring |
| title_short | Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring |
| title_sort | excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring |
| topic | DVC® DMSXL DM1 digital biomarker sleep excessive daytime sleepiness (EDS) |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1130055/full |
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