Abstract
Dystrophinopathy is caused by mutations in the dystrophin gene, which lead to progressive muscle degeneration, necrosis, and finally, death. Recently, golden retrievers have been suggested as a useful animal model for studying human dystrophinopathy, but the model has limitations due to difficulty in maintaining the genetic background using conventional breeding. In this study, we successfully generated a dystrophin mutant dog using the CRISPR/Cas9 system and somatic cell nuclear transfer. The dystrophin mutant dog displayed phenotypes such as elevated serum creatine kinase, dystrophin deficiency, skeletal muscle defects, an abnormal electrocardiogram, and avoidance of ambulation. These results indicate that donor cells with CRISPR/Cas9 for a specific gene combined with the somatic cell nuclear transfer technique can efficiently produce a dystrophin mutant dog, which will help in the successful development of gene therapy drugs for dogs and humans.
Highlights
Canis familiaris has drawn considerable attention as a model for investigating human diseases
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most common X-linked recessive muscular dystrophies caused by mutations in the dystrophin gene leading to a defective dystrophin–glycoprotein complex [3]
Having confirmed that Cas9/sgRNA was highly active in cultured cells, we performed Somatic cell nuclear transfer (SCNT) to generate a dystrophin mutant dog
Summary
Canis familiaris has drawn considerable attention as a model for investigating human diseases. Dogs show over 450 naturally occurring diseases, of which approximately 360 are analogous to human diseases [1] Based on their size, biological features, and ease of behavioral evaluation and handling, dogs can be good animal models. DMD and BMD are classified as dystrophinopathies because they are caused by alterations in the dystrophin gene These mutations lead to progressive muscle degeneration and, to necrosis [3,4]. This can result in substantial physical and locomotor deficits, leading to the need for wheelchair use and early death due to heart failure. Both laboratory-generated and naturally occurring animal models are available to study the pathogenesis of dystrophinopathy and to develop potential new treatments [5]. Mdx mice exhibit minimal clinical symptoms and have only a 25% reduction in longevity, unlike DMD patients, who have a
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
