Molecular and Phenotypic Changes in FLExDUX4 Mice
Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (<i>DUX4</i>) gene. The <i>FLExDUX4</i> mouse model carries an inverted human <i>DUX4</i> transgene which has leaky <i>DUX4</i> transgene expres...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/7/1040 |
| _version_ | 1797588703208538112 |
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| author | Kelly Murphy Aiping Zhang Adam J. Bittel Yi-Wen Chen |
| author_facet | Kelly Murphy Aiping Zhang Adam J. Bittel Yi-Wen Chen |
| author_sort | Kelly Murphy |
| collection | DOAJ |
| description | Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (<i>DUX4</i>) gene. The <i>FLExDUX4</i> mouse model carries an inverted human <i>DUX4</i> transgene which has leaky <i>DUX4</i> transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the <i>FLExDUX4</i> phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male <i>FLExDUX4</i> mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the <i>FLExDUX4</i> mice. |
| first_indexed | 2024-03-11T00:55:46Z |
| format | Article |
| id | doaj.art-76a673f6f43340e4a0d8aa05366622fc |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T00:55:46Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-76a673f6f43340e4a0d8aa05366622fc2023-11-18T20:02:41ZengMDPI AGJournal of Personalized Medicine2075-44262023-06-01137104010.3390/jpm13071040Molecular and Phenotypic Changes in FLExDUX4 MiceKelly Murphy0Aiping Zhang1Adam J. Bittel2Yi-Wen Chen3Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USACenter for Genetic Medicine Research, Children’s National Hospital, Washington, DC 20010, USACenter for Genetic Medicine Research, Children’s National Hospital, Washington, DC 20010, USAInstitute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USAFacioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (<i>DUX4</i>) gene. The <i>FLExDUX4</i> mouse model carries an inverted human <i>DUX4</i> transgene which has leaky <i>DUX4</i> transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the <i>FLExDUX4</i> phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male <i>FLExDUX4</i> mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the <i>FLExDUX4</i> mice.https://www.mdpi.com/2075-4426/13/7/1040facioscapulohumeralmusculardystrophyFSHD<i>FLExDUX4</i>DUX4 |
| spellingShingle | Kelly Murphy Aiping Zhang Adam J. Bittel Yi-Wen Chen Molecular and Phenotypic Changes in FLExDUX4 Mice Journal of Personalized Medicine facioscapulohumeral muscular dystrophy FSHD <i>FLExDUX4</i> DUX4 |
| title | Molecular and Phenotypic Changes in FLExDUX4 Mice |
| title_full | Molecular and Phenotypic Changes in FLExDUX4 Mice |
| title_fullStr | Molecular and Phenotypic Changes in FLExDUX4 Mice |
| title_full_unstemmed | Molecular and Phenotypic Changes in FLExDUX4 Mice |
| title_short | Molecular and Phenotypic Changes in FLExDUX4 Mice |
| title_sort | molecular and phenotypic changes in flexdux4 mice |
| topic | facioscapulohumeral muscular dystrophy FSHD <i>FLExDUX4</i> DUX4 |
| url | https://www.mdpi.com/2075-4426/13/7/1040 |
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