{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T02:12:45Z","timestamp":1769739165467,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071575"],"award-info":[{"award-number":["82071575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20ZR1435100"],"award-info":[{"award-number":["20ZR1435100"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["18411964500"],"award-info":[{"award-number":["18411964500"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["16ZR1422000"],"award-info":[{"award-number":["16ZR1422000"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["18YF1415700"],"award-info":[{"award-number":["18YF1415700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2020YJZX0122"],"award-info":[{"award-number":["2020YJZX0122"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It has been observed that Slo1 knockout mice have reduced motor function, and people with certain Slo1 mutations have movement problems, but there is no answer whether the movement disorder is caused by the loss of Slo1 in the nervous system, or skeletal muscle, or both. Here, to ascertain in which tissues Slo1 functions to regulate motor function and offer deeper insight in treating related movement disorder, we generated skeletal muscle\u2010specific Slo1 knockout mice, studied the functional changes in Slo1\u2010deficient skeletal muscle and explored the underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used skeletal muscle\u2010specific Slo1 knockout mice (Myf5\u2010Cre; Slo1<jats:sup>flox\/flox<\/jats:sup> mice, called CKO) as in vivo models to examine the role of Slo1 in muscle growth and muscle regeneration. The forelimb grip strength test was used to assess skeletal muscle function and treadmill exhaustion test was used to test whole\u2010body endurance. Mouse primary myoblasts derived from CKO (myoblast\/CKO) mice were used to extend the findings to in vitro effects on myoblast differentiation and fusion. Quantitative real\u2010time PCR, western blot and immunofluorescence approaches were used to analyse Slo1 expression during myoblast differentiation and muscle regeneration. To investigate the involvement of genes in the regulation of muscle dysfunction induced by Slo1 deletion, RNA\u2010seq analysis was performed in primary myoblasts. Immunoprecipitation and mass spectrometry were used to identify the protein interacting with Slo1. A dual\u2010luciferase reporter assay was used to identify whether Slo1 deletion affects NFAT activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the body weight and size of CKO mice were not significantly different from those of Slo1<jats:sup>flox\/flox<\/jats:sup> mice (called WT). Deficiency of Slo1 in muscles leads to reduced endurance (~30% reduction, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and strength (~30% reduction, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Although there was no difference in the general morphology of the muscles, electron microscopy revealed a considerable reduction in the content of mitochondria in the soleus muscle (~40% reduction, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). We found that Slo1 was expressed mainly on the cell membrane and showed higher expression in slow\u2010twitch fibres. Slo1 protein expression is progressively reduced during muscle postnatal development and regeneration after injury, and the expression is strongly reduced during myoblast differentiation. Slo1 deletion impaired myoblast differentiation and slow\u2010twitch fibre formation. Mechanistically, RNA\u2010seq analysis showed that Slo1 influences the expression of genes related to myogenic differentiation and slow\u2010twitch fibre formation. Slo1 interacts with FAK to influence myogenic differentiation, and Slo1 deletion diminishes NFAT activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data reveal that Slo1 deficiency impaired skeletal muscle regeneration and slow\u2010twitch fibre formation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13253","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T07:59:56Z","timestamp":1684742396000},"page":"1737-1752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Slo1 deficiency impaired skeletal muscle regeneration and slow\u2010twitch fibre formation"],"prefix":"10.1002","volume":"14","author":[{"given":"Chao","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Geriatrics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinrun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-4855","authenticated-orcid":false,"given":"Yanhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Geriatrics Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  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