| Autor: |
Langer, Henning T, Mossakowski, Agata A, Willis, Brandon J, Grimsrud, Kristin N, Wood, Joshua A, Lloyd, Kevin CK, Zbinden-Foncea, Hermann, Baar, Keith |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Journal of cachexia, sarcopenia and muscle, vol 11, iss 5 |
| Popis: |
BackgroundDesminopathy is a clinically heterogeneous muscle disease caused by over 60 different mutations in desmin. The most common mutation with a clinical phenotype in humans is an exchange of arginine to proline at position 350 of desmin leading to p.R350P. We created the first CRISPR-Cas9 engineered rat model for a muscle disease by mirroring the R350P mutation in humans.MethodsUsing CRISPR-Cas9 technology, Des c.1045-1046 (AGG>CCG) was introduced into exon 6 of the rat genome causing p.R349P. The genotype of each animal was confirmed via quantitative PCR. Six male rats with a mutation in desmin (n=6) between the age of 120-150days and an equal number of wild type littermates (n=6) were used for experiments. Maximal plantar flexion force was measured in vivo and combined with the collection of muscle weights, immunoblotting, and histological analysis. In addition to the baseline phenotyping, we performed a synergist ablation study in the same animals.ResultsWe found a difference in the number of central nuclei between desmin mutants (1±0.4%) and wild type littermates (0.2±0.1%; P |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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