Generation of a Dystrophin Mutant in Dog by Nuclear Transfer Using CRISPR/Cas9-Mediated Somatic Cells: A Preliminary Study

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 i...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-03, Vol.23 (5), p.2898
Main Authors: Oh, Hyun Ju, Chung, Eugene, Kim, Jaehwan, Kim, Min Jung, Kim, Geon A, Lee, Seok Hee, Ra, Kihae, Eom, Kidong, Park, Soojin, Chae, Jong-Hee, Kim, Jin-Soo, Lee, Byeong Chun
Format: Article
Language:English
Subjects:
Age
Animal models
Animals
Cloning
Creatine
Creatine kinase
CRISPR
CRISPR-Cas Systems - genetics
CRISPR/Cas9
Degeneration
Disease
dog
Dogs
Drug development
Dystrophin
Dystrophin - genetics
Dystrophin - metabolism
EKG
Electrocardiography
Gene Editing
Gene therapy
Genes
Genomes
Kinases
Magnetic resonance imaging
Muscle, Skeletal - metabolism
Muscles
Muscular dystrophy
Muscular Dystrophy, Duchenne - genetics
Muscular Dystrophy, Duchenne - therapy
mutant
Mutants
Mutation
Necrosis
Nuclear transfer
Nuclear Transfer Techniques
Phenotypes
Skeletal muscle
Somatic cell nuclear transfer
Somatic cells
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23052898