RGD Reference Report - Generation of muscular dystrophy model rats with a CRISPR/Cas system. - Rat Genome Database

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Generation of muscular dystrophy model rats with a CRISPR/Cas system.

Authors: Nakamura, K  Fujii, W  Tsuboi, M  Tanihata, J  Teramoto, N  Takeuchi, S  Naito, K  Yamanouchi, K  Nishihara, M 
Citation: Nakamura K, etal., Sci Rep. 2014 Jul 9;4:5635. doi: 10.1038/srep05635.
RGD ID: 11040981
Pubmed: PMID:25005781   (View Abstract at PubMed)
PMCID: PMC4088098   (View Article at PubMed Central)
DOI: DOI:10.1038/srep05635   (Journal Full-text)

Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin. DMD model animals, such as mdx mice and canine X-linked muscular dystrophy dogs, have been widely utilized in the development of a treatment for DMD. Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats. We simultaneously targeted two exons in the rat Dmd gene, which resulted in the absence of Dystrophin expression in the F0 generation. Dmd-mutated rats exhibited a decline in muscle strength, and the emergence of degenerative/regenerative phenotypes in the skeletal muscle, heart, and diaphragm. These mutations were heritable by the next generation, and F1 male rats exhibited similar phenotypes in their skeletal muscles. These model rats should prove to be useful for developing therapeutic methods to treat DMD.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Duchenne muscular dystrophy  ISODmd (Rattus norvegicus)11040981; 11040981 RGD 
Duchenne muscular dystrophy  IMP 11040981; 11040981 RGD 
Duchenne muscular dystrophy MODEL: spontaneousIMP 11040981 RGD 

Phenotype Annotations    Click to see Annotation Detail View
Objects Annotated

Genes (Rattus norvegicus)
Dmd  (dystrophin)
Dmdem1Kykn  (dystrophin; CRISPR/Cas9 system induced mutant 1, Keitaro Yamanouchi)

Genes (Mus musculus)
Dmd  (dystrophin, muscular dystrophy)

Genes (Homo sapiens)
DMD  (dystrophin)

Strains
W-Dmdem1Kykn  (NA)

Objects referenced in this article
Strain W-Dmdem2Kykn null Rattus norvegicus
Strain W-Dmdem3Kykn null Rattus norvegicus

Additional Information