Sustaining Cardiac Claudin-5 Levels Prevents Functional Hallmarks of Cardiomyopathy in a Muscular Dystrophy Mouse Model

A recently discovered mouse model (‘mdx’) for muscular dystrophy in man may be of considerable interest, since the disease in ‘mdx’ mice is inherited by the same mode of inheritance (X-linked) as the human Duchenne (DMD) muscular dystrophy. Unlike DMD, which results in a situation in which the continual muscle destruction cannot keep up with abortive regenerative attempts of the musculature, and the sufferers of the disease die early, the disease in ‘mdx’ mice appears to be transient, and the mice do not die as a result of it. In fact, it has been reported that the severely damaged Tibialis anterior (TA) muscles of ‘mdx’ mice seem to display exceptionally good regenerative powers at 4-6 weeks, so much so, that these muscles are able to regenerate spontaneously up to their previous levels of physiological activity.

Download Full-text

Faculty Opinions recommendation of Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725255143.793521792 ◽

2016 ◽

Author(s):

George Dickson

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Single Peptide

Download Full-text

VEGFR-1/Flt-1 Inhibition Increases Angiogenesis and Improves Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy

Molecular Therapy — Methods & Clinical Development ◽

10.1016/j.omtm.2021.03.013 ◽

2021 ◽

Author(s):

Jennifer Bosco ◽

Zhiwei Zhou ◽

Sofie Gabriëls ◽

Mayank Verma ◽

Nan Liu ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Muscle Function

Download Full-text

TENASCIN C PROMOTES ENDOTHELIAL DYSFUNCTION ACCOMPANIED WITH CARDIAC FIBROSIS IN A MOUSE MODEL OF DUCHENNE MUSCULAR DYSTROPHY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)02200-2 ◽

2021 ◽

Vol 77 (18) ◽

pp. 841

Author(s):

Petra Lujza Szabo ◽

Ouafa Hamza ◽

Milat Inci ◽

Janine Ebner ◽

Karlheinz Hilber ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Endothelial Dysfunction ◽

Muscular Dystrophy ◽

Mouse Model ◽

Cardiac Fibrosis ◽

Tenascin C

Download Full-text

In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers

Genome Medicine ◽

10.1186/s13073-021-00876-0 ◽

2021 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Menglong Chen ◽

Hui Shi ◽

Shixue Gou ◽

Xiaomin Wang ◽

Lei Li ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Genome Editing ◽

Large Scale ◽

Gene Editing ◽

High Efficiency ◽

Muscle Fibers ◽

Muscle Cells

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

Download Full-text