著者

Jun Tanihata Shin’ichi Takeda

出版者

一般社団法人日本体力医学会

雑誌

The Journal of Physical Fitness and Sports Medicine (ISSN:21868131)

巻号頁・発行日

vol.5, no.4, pp.309-312, 2016-09-25 (Released:2016-10-03)

参考文献数

38

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Duchenne muscular dystrophy (DMD) is a life-limiting X-linked genetic disorder caused by a lack of the membrane-associated protein dystrophin. The absence of dystrophin increases the susceptibility of muscle fibers to damage. Repeated damage results in ineffective muscle repair and the development of pseudo-hypertrophied muscles; these bulky muscles are weak despite their size. The mechanisms underlying the functional impairments in dystrophic muscle have not yet been fully determined. However, several recent studies indicate that elevated intracellular Ca2+ homeostasis is a cause or facilitator of the development of muscle weakness in DMD. This review focuses on abnormalities of Ca2+ homeostasis and the possibilities for treatment by counteracting the Ca2+ dysregulation.

著者

Hidetoshi Sugihara Koichi Kimura Keitaro Yamanouchi Naomi Teramoto Tomoko Okano Masao Daimon Hiroyuki Morita Katsu Takenaka Takanori Shiga Jun Tanihata Yoshitsugu Aoki Tokiko Inoue-Nagamura Hiroshi Yotsuyanagi Issei Komuro

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

pp.20-372, (Released:2020-11-13)

参考文献数

25

被引用文献数

9

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Duchenne muscular dystrophy (DMD) is X-linked recessive myopathy caused by mutations in the dystrophin gene. Although conventional treatments have improved their prognosis, inevitable progressive cardiomyopathy is still the leading cause of death in patients with DMD. To explore novel therapeutic options, a suitable animal model with heart involvement has been warranted.We have generated a rat model with an out-of-frame mutation in the dystrophin gene using CRISPR/Cas9 genome editing (DMD rats). The aim of this study was to evaluate their cardiac functions and pathologies to provide baseline data for future experiments developing treatment options for DMD.In comparison with age-matched wild rats, 6-month-old DMD rats showed no significant differences by echocardiographic evaluations. However, 10-month-old DMD rats showed significant deterioration in left ventricular (LV) fractional shortening (P = 0.024), and in tissue Doppler peak systolic velocity (Sa) at the LV lateral wall (P = 0.041) as well as at the right ventricular (RV) free-wall (P = 0.004). These functional findings were consistent with the fibrotic distributions by histological analysis.Although the cardiac phenotype was milder than anticipated, DMD rats showed similar distributions and progression of heart involvement to those of patients with DMD. This animal may be a useful model with which to develop effective drugs and to understand the underlying mechanisms of progressive heart failure in patients with DMD.