Dystrophin deficiency impairs vascular structure and function in the canine model of Duchenne muscular dystrophy

2021 ◽  
Author(s):  
Kasun Kodippili ◽  
Pamela K Thorne ◽  
M. Harold Laughlin ◽  
Dongsheng Duan
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Canine Model ◽  
Structure And Function ◽  
Vascular Structure ◽  
Dystrophin Deficiency ◽  
And Function

scholarly journals Validation of DE50-MD dogs as a model for the brain phenotype of Duchenne muscular dystrophy

2022 ◽  
Author(s):  
Abbe H. Crawford ◽  
John C.W. Hildyard ◽  
Sophie A.M. Rushing ◽  
Dominic J. Wells ◽  
Maria Diez-Leon ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Canine Model ◽  
Clinical Model ◽  
Dystrophin Expression ◽  
Canine Brain ◽  
Dystrophin Deficiency ◽  
Novel Objects ◽  
And Function ◽  
The Brain

Duchenne muscular dystrophy (DMD), a fatal musculoskeletal disorder, is associated with neurodevelopmental disorders and cognitive impairment caused by brain dystrophin deficiency. Dog models of DMD represent key translational tools to study dystrophin biology and to develop novel therapeutics. However, characterization of dystrophin expression and function in the canine brain is lacking. We studied the DE50-MD canine model of DMD that has a missense mutation in the donor splice site of exon 50. Using a battery of cognitive tests, we detected a neurocognitive phenotype in DE50-MD dogs including reduced attention, problem-solving and exploration of novel objects. Through a combination of capillary immunoelectrophoresis, immunolabelling, qPCR and RNAScope in situ hybridization we show that regional dystrophin expression in the adult canine brain reflects that of humans, and that the DE50-MD dog lacks full length dystrophin (Dp427) protein expression but retains expression of the two shorter brain-expressed isoforms, Dp140 and Dp71. Thus, the DE50-MD dog is a translationally-relevant pre-clinical model to study the consequences of Dp427 deficiency in the brain and to develop therapeutic strategies for the neurological sequelae of DMD.

Cardiac structure and function in female carriers of a canine model of Duchenne muscular dystrophy

2013 ◽  
Vol 94 (3) ◽  
pp. 610-617 ◽  
Author(s):  
A.M. Kane ◽  
T.C. DeFrancesco ◽  
M.C. Boyle ◽  
D.E. Malarkey ◽  
J.W. Ritchey ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Canine Model ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Cardiac Structure And Function ◽  
And Function ◽  
Female Carriers

scholarly journals Dystrophin Deficiency Compromises Force Production of the Extensor Carpi Ulnaris Muscle in the Canine Model of Duchenne Muscular Dystrophy

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44438 ◽  
Author(s):  
Hsiao T. Yang ◽  
Jin-Hong Shin ◽  
Chady H. Hakim ◽  
Xiufang Pan ◽  
Ronald L. Terjung ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Force Production ◽  
Canine Model ◽  
Extensor Carpi Ulnaris ◽  
Dystrophin Deficiency

scholarly journals Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy

2018 ◽  
Vol 114 ◽  
pp. 345-353 ◽  
Author(s):  
Younss Ait Mou ◽  
Alain Lacampagne ◽  
Thomas Irving ◽  
Valérie Scheuermann ◽  
Stéphane Blot ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Structure And Function ◽  
And Function ◽  
Duchenne Muscular Dystrophy Cardiomyopathy

scholarly journals Altered Myofilament Structure and Function in Dogs with Duchenne Muscular Dystrophy Cardiomyopathy

2016 ◽  
Author(s):  
Younss Ait Mou ◽  
Alain Lacampagne ◽  
Thomas C Irving ◽  
Stéphane Blot ◽  
Bijan Ghaleh-Marzban ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Structure And Function ◽  
And Function ◽  
Duchenne Muscular Dystrophy Cardiomyopathy

scholarly journals Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Science ◽  
2018 ◽  
Vol 362 (6410) ◽  
pp. 86-91 ◽  
Author(s):  
Leonela Amoasii ◽  
John C. W. Hildyard ◽  
Hui Li ◽  
Efrain Sanchez-Ortiz ◽  
Alex Mireault ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gene Editing ◽  
Canine Model ◽  
Large Animal ◽  
Systemic Delivery ◽  
Gene Encoding ◽  
Animal Data ◽  
And Function ◽  
Dystrophin Protein

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD.

Reduced Hedgehog signalling in Duchenne muscular dystrophy impairs muscle regeneration and function

2017 ◽  
Vol 27 ◽  
pp. S13
Author(s):  
S. Devenport ◽  
C.M. Penton ◽  
N. Salgado ◽  
H. Wang ◽  
K. Flanigan ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Regeneration ◽  
Hedgehog Signalling ◽  
And Function
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