Details

Autor(en) / Beteiligte

• Okamoto, Kazutoshi
• Matsunari, Hitomi
• Nakano, Kazuaki
• Umeyama, Kazuhiro
• Hasegawa, Koki
• Uchikura, Ayuko
• Takayanagi, Shuko
• Watanabe, Masahito
• Ohgane, Jun
• Stirm, Michael
• Kurome, Mayuko
• Klymiuk, Nikolai
• Nagaya, Masaki
• Wolf, Eckhard
• Nagashima, Hiroshi

Titel

Phenotypic features of genetically modified DMD-XKOXWT pigs

Ist Teil von

• Regenerative therapy, 2023-12, Vol.24, p.451-458

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder caused by mutation in the dystrophin gene (DMD) on the X chromosome. Female DMD carriers occasionally exhibit symptoms such as muscle weakness and heart failure. Here, we investigated the characteristics and representativeness of female DMD carrier (DMD-XKOXWT) pigs as a suitable disease model. In vitro fertilization using sperm from a DMD-XKOY↔XWTXWT chimeric boar yielded DMD-XKOXWT females, which were used to generate F2 and F3 progeny, including DMD-XKOXWT females. F1–F3 piglets were genotyped and subjected to biochemical analysis for blood creatine kinase (CK), aspartate aminotransferase, and lactate dehydrogenase. Skeletal muscle and myocardial tissue were analyzed for the expression of dystrophin and utrophin, as well as for lymphocyte and macrophage infiltration. DMD-XKOXWT pigs exhibited various characteristics common to human DMD carrier patients, namely, asymptomatic hyperCKemia, dystrophin expression patterns in the skeletal and cardiac muscles, histopathological features of skeletal muscle degeneration, myocardial lesions in adulthood, and sporadic death. Pathological abnormalities observed in the skeletal muscles in DMD-XKOXWT pigs point to a frequent incidence of pathological abnormalities in the musculoskeletal tissues of latent DMD carriers. Our findings suggest a higher risk of myocardial abnormalities in DMD carrier women than previously believed. We demonstrated that DMD-XKOXWT pigs could serve as a suitable large animal model for understanding the pathogenic mechanism in DMD carriers and developing therapies for female DMD carriers. •DMD carrier model pigs were produced using artificial reproductive technologies.•DMD-XKOXWT pigs share various characteristics with DMD carrier patients.•Myocardial fibrosis in DMD-XKOXWT pigs may underlie cardiac incompetency in carriers.