{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:08:33Z","timestamp":1790690913021,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["16-15-10178"],"award-info":[{"award-number":["16-15-10178"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Laminopathies are a family of monogenic multi-system diseases resulting from mutations in the LMNA gene which include a wide range of neuromuscular disorders. Although lamins are expressed in most types of differentiated cells, LMNA mutations selectively affect only specific tissues by mechanisms that remain largely unknown. We have employed the combination of functional in vitro experiments and transcriptome analysis in order to determine how two LMNA mutations associated with different phenotypes affect skeletal muscle development and metabolism. We used a muscle differentiation model based on C2C12 mouse myoblasts genetically modified with lentivirus constructs bearing wild-type human LMNA (WT-LMNA) or R482L-LMNA\/G232E-LMNA mutations, linked to familial partial lipodystrophy of the Dunnigan type and muscular dystrophy phenotype accordingly. We have shown that both G232E\/R482L-LMNA mutations cause dysregulation in coordination of pathways that control cell cycle dynamics and muscle differentiation. We have also found that R482\/G232E-LMNA mutations induce mitochondrial uncoupling and a decrease in glycolytic activity in differentiated myotubes. Both types of alterations may contribute to mutation-induced muscle tissue pathology.<\/jats:p>","DOI":"10.3390\/genes11091057","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T09:18:16Z","timestamp":1599470296000},"page":"1057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["LMNA Mutations G232E and R482L Cause Dysregulation of Skeletal Muscle Differentiation, Bioenergetics, and Metabolic Gene Expression Profile"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-6562","authenticated-orcid":false,"given":"Elena V.","family":"Ignatieva","sequence":"first","affiliation":[{"name":"National Almazov Medical Research Centre, Institute of Molecular Biology and Genetics, 197341 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-2162","authenticated-orcid":false,"given":"Oksana A.","family":"Ivanova","sequence":"additional","affiliation":[{"name":"National Almazov Medical Research Centre, Institute of Molecular Biology and Genetics, 197341 Saint-Petersburg, Russia"},{"name":"ITMO University, Information Technologies and Programming Faculty, International Laboratory of Bioinformatics and Genomics, 197101 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7520-090X","authenticated-orcid":false,"given":"Margarita Y.","family":"Komarova","sequence":"additional","affiliation":[{"name":"National Almazov Medical Research Centre, Institute of Molecular Biology and Genetics, 197341 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia V.","family":"Khromova","sequence":"additional","affiliation":[{"name":"National Almazov Medical Research Centre, Institute of Molecular Biology and Genetics, 197341 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-2791","authenticated-orcid":false,"given":"Dmitrii E.","family":"Polev","sequence":"additional","affiliation":[{"name":"Research Resource Center \u201cBiobank\u201d, St Petersburg State University, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A.","family":"Kostareva","sequence":"additional","affiliation":[{"name":"National Almazov Medical Research Centre, Institute of Molecular Biology and Genetics, 197341 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Sergushichev","sequence":"additional","affiliation":[{"name":"ITMO University, Information Technologies and Programming Faculty, International Laboratory of Bioinformatics and Genomics, 197101 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3073-7914","authenticated-orcid":false,"given":"Renata I.","family":"Dmitrieva","sequence":"additional","affiliation":[{"name":"National Almazov Medical Research Centre, Institute of Molecular Biology and Genetics, 197341 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/1531-8249(200008)48:2<170::AID-ANA6>3.0.CO;2-J","article-title":"Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A\/C gene","volume":"48","author":"Bonne","year":"2000","journal-title":"Ann. 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