Generation and characterization of a novel mouse model of Becker Muscular Dystrophy with a deletion of exons 52 to 55.

Autor:	Perillat LOM; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada., Wong TWY; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada., Maino E; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada., Ahmed A; Department of Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada., Scott O; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.; Division of Immunology and Allergy, Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada., Hyatt E; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada., Delgado-Olguin P; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.; Heart & Stroke Richard Lewar Centre of Excellence, Toronto, ON, Canada., Visuvanathan S; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada., Ivakine EA; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Cohn RD; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.; Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.; Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2024 Aug 05. Date of Electronic Publication: 2024 Aug 05.
DOI:	10.1242/dmm.050595
Abstrakt:	Becker Muscular Dystrophy (BMD) is a rare X-linked recessive neuromuscular disorder frequently caused by in-frame deletions in the DMD gene that result in the production of a truncated, yet functional, dystrophin protein. The consequences of BMD-causing in-frame deletions on the organism are difficult to predict, especially in regard to long-term prognosis. Here, we employed CRISPR-Cas9 to generate a new Dmd del52-55 mouse model by deleting exons 52-55, resulting in a BMD-like in-frame deletion. To delineate the long-term effects of this deletion, we studied these mice over 52 weeks by performing histology and echocardiography analyses and assessing motor functions. Our results suggest that a truncated dystrophin is sufficient to maintain wildtype-like muscle and heart histology and functions in young mice. However, the truncated protein appears insufficient to maintain normal muscle homeostasis and protect against exercise-induced damage at 52 weeks. To further delineate the effects of this exon52-55 in-frame deletion, we performed RNA-Seq pre- and post-exercise and identified several differentially expressed pathways that reflect the abnormal muscle phenotype observed at 52 weeks in the BMD model. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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