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In-Frame Deletion of Dystrophin Exons 8–50 Results in DMD Phenotypeстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 февраля 2024 г.
- Авторы: Egorova Tatiana V., Galkin Ivan I., Velyaev Oleg A., Vassilieva Svetlana G., Savchenko Irina M., Loginov Vyacheslav A., Dzhenkova Marina A., Korshunova Diana S., Kozlova Olga S., Ivankov Dmitry N., Polikarpova Anna V.
- Журнал: International Journal of Molecular Sciences
- Том: 24
- Номер: 11
- Год издания: 2023
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 9117
- Последняя страница: 9117
- DOI: 10.3390/ijms24119117
- Аннотация: Mutations that prevent the production of proteins in the DMD gene cause Duchenne muscular dystrophy. Most frequently, these are deletions leading to reading-frame shift. The "reading-frame rule" states that deletions that preserve ORF result in a milder Becker muscular dystrophy. By removing several exons, new genome editing tools enable reading-frame restoration in DMD with the production of BMD-like dystrophins. However, not every truncated dystrophin with a significant internal loss functions properly. To determine the effectiveness of potential genome editing, each variant should be carefully studied in vitro or in vivo. In this study, we focused on the deletion of exons 8-50 as a potential reading-frame restoration option. Using the CRISPR-Cas9 tool, we created the novel mouse model DMDdel8-50, which has an in-frame deletion in the DMD gene. We compared DMDdel8-50 mice to C57Bl6/CBA background control mice and previously generated DMDdel8-34 KO mice. We discovered that the shortened protein was expressed and correctly localized on the sarcolemma. The truncated protein, on the other hand, was unable to function like a full-length dystrophin and prevent disease progression. On the basis of protein expression, histological examination, and physical assessment of the mice, we concluded that the deletion of exons 8-50 is an exception to the reading-frame rule.
- Добавил в систему: Галкин Иван Ильич