Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles
Yuri Yamashita,
Satoshi Nakada,
Kyoko Nakamura,
Hidetoshi Sakurai,
Kinji Ohno,
Tomohide Goto,
Yo Mabuchi,
Chihiro Akazawa,
Nobutaka Hattori,
Eri Arikawa-Hirasawa
Affiliations
Yuri Yamashita
Aging Biology in Health and Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Satoshi Nakada
Japanese Center for Research on Women in Sport, Juntendo University Graduate School of Health and Sports Science, Chiba 270-1695, Japan
Kyoko Nakamura
Department of Physiology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Hidetoshi Sakurai
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
Kinji Ohno
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Tomohide Goto
Department of Neurology, Kanagawa Children’s Medical Center, Yokohama 232-8555, Japan
Yo Mabuchi
Intractable Disease Research Centre, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Chihiro Akazawa
Intractable Disease Research Centre, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Nobutaka Hattori
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan
Eri Arikawa-Hirasawa
Aging Biology in Health and Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
Schwartz–Jampel syndrome (SJS) is an autosomal recessive disorder caused by loss-of-function mutations in heparan sulfate proteoglycan 2 (HSPG2), which encodes the core basement membrane protein perlecan. Myotonia is a major criterion for the diagnosis of SJS; however, its evaluation is based solely on physical examination and can be challenging in neonates and young children. Furthermore, the pathomechanism underlying SJS-related myotonia is not fully understood, and effective treatments for SJS are limited. Here, we established a cellular model of SJS using patient-derived human-induced pluripotent stem cells. This model exhibited hyper-responsiveness to acetylcholine as a result of abnormalities in the perlecan molecule, which were confirmed via comparison of their calcium imaging with calcium imaging of satellite cells derived from Hspg2−/−-Tg mice, which exhibit myotonic symptoms similar to SJS symptoms. Therefore, our results confirm the utility of creating cellular models for investigating SJS and their application in evaluating myotonia in clinical cases, while also providing a useful tool for the future screening of SJS therapies.
