Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology
Summary: Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) have been identified in patients suffering from various degenerative diseases including mitochondrial myopathy, spinal muscular atrophy Jokela type, frontotemporal dementia, and/or amyotrophic lateral sclerosis...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221000298 |
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| author | Éanna B. Ryan Jianhua Yan Nimrod Miller Sudarshan Dayanidhi Yongchao C. Ma Han-Xiang Deng Teepu Siddique |
| author_facet | Éanna B. Ryan Jianhua Yan Nimrod Miller Sudarshan Dayanidhi Yongchao C. Ma Han-Xiang Deng Teepu Siddique |
| author_sort | Éanna B. Ryan |
| collection | DOAJ |
| description | Summary: Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) have been identified in patients suffering from various degenerative diseases including mitochondrial myopathy, spinal muscular atrophy Jokela type, frontotemporal dementia, and/or amyotrophic lateral sclerosis (ALS). The pathogenic mechanism underlying CHCHD10-linked divergent disorders remains largely unknown. Here we show that transgenic mice overexpressing an ALS-linked CHCHD10 p.R15L mutation leads to an abbreviated lifespan compared with CHCHD10-WT transgenic mice. The occurrence and severity of the phenotype correlates to transgene copy number. Central nervous system (CNS), skeletal muscle, and cardiac pathology is apparent in CHCHD10-R15L transgenic mice. Despite the pathology, CHCHD10-R15L transgenic mice perform comparably to control mice in motor behavioral tasks until very close to death. Although paralysis is not observed, these models provide insight into the pleiotropic nature of CHCHD10 and suggest a contribution of CNS, skeletal muscle, and cardiac pathology to CHCHD10 p.R15L-ALS pathogenesis. |
| first_indexed | 2024-12-19T12:25:19Z |
| format | Article |
| id | doaj.art-33aca3422669407a9e11c79ae56d769e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-19T12:25:19Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-33aca3422669407a9e11c79ae56d769e2022-12-21T20:21:34ZengElsevieriScience2589-00422021-02-01242102061Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathologyÉanna B. Ryan0Jianhua Yan1Nimrod Miller2Sudarshan Dayanidhi3Yongchao C. Ma4Han-Xiang Deng5Teepu Siddique6The Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Tarry Building, Room 13-715, 303 East Chicago Avenue, Chicago, IL 60611, USA; Northwestern University Interdepartmental Neuroscience Program, Chicago, IL, USAThe Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Tarry Building, Room 13-715, 303 East Chicago Avenue, Chicago, IL 60611, USAAnn and Robert H. Lurie Children's Hospital of Chicago and Departments of Pediatrics, Neurology and Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAShirley Ryan AbilityLab and Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAnn and Robert H. Lurie Children's Hospital of Chicago and Departments of Pediatrics, Neurology and Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAThe Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Tarry Building, Room 13-715, 303 East Chicago Avenue, Chicago, IL 60611, USAThe Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Tarry Building, Room 13-715, 303 East Chicago Avenue, Chicago, IL 60611, USA; Northwestern University Interdepartmental Neuroscience Program, Chicago, IL, USA; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Corresponding authorSummary: Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) have been identified in patients suffering from various degenerative diseases including mitochondrial myopathy, spinal muscular atrophy Jokela type, frontotemporal dementia, and/or amyotrophic lateral sclerosis (ALS). The pathogenic mechanism underlying CHCHD10-linked divergent disorders remains largely unknown. Here we show that transgenic mice overexpressing an ALS-linked CHCHD10 p.R15L mutation leads to an abbreviated lifespan compared with CHCHD10-WT transgenic mice. The occurrence and severity of the phenotype correlates to transgene copy number. Central nervous system (CNS), skeletal muscle, and cardiac pathology is apparent in CHCHD10-R15L transgenic mice. Despite the pathology, CHCHD10-R15L transgenic mice perform comparably to control mice in motor behavioral tasks until very close to death. Although paralysis is not observed, these models provide insight into the pleiotropic nature of CHCHD10 and suggest a contribution of CNS, skeletal muscle, and cardiac pathology to CHCHD10 p.R15L-ALS pathogenesis.http://www.sciencedirect.com/science/article/pii/S2589004221000298Molecular PhysiologyMolecular BiologyNeuroscience |
| spellingShingle | Éanna B. Ryan Jianhua Yan Nimrod Miller Sudarshan Dayanidhi Yongchao C. Ma Han-Xiang Deng Teepu Siddique Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology iScience Molecular Physiology Molecular Biology Neuroscience |
| title | Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology |
| title_full | Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology |
| title_fullStr | Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology |
| title_full_unstemmed | Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology |
| title_short | Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology |
| title_sort | early death of als linked chchd10 r15l transgenic mice with central nervous system skeletal muscle and cardiac pathology |
| topic | Molecular Physiology Molecular Biology Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221000298 |
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