{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:00:26Z","timestamp":1773288026661,"version":"3.50.1"},"publisher-location":"New York, NY","reference-count":8,"publisher":"Springer US","isbn-type":[{"value":"9781071620090","type":"print"},{"value":"9781071620106","type":"electronic"}],"license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a rare genetic disease affecting 1 in 5000 newborn boys. It is caused by mutations in the <jats:italic>DMD<\/jats:italic> gene with a consequent lack of dystrophin protein that leads to deterioration of myofibers and their replacement with fibro-adipogenic tissue. Using antisense oligonucleotides (AONs) to modify out-of-frame mutations in the <jats:italic>DMD<\/jats:italic> gene, named exon skipping, is currently considered among the most promising treatments for DMD patients. The development of this strategy is rapidly moving forward, and AONs designed to skip exons 51 and 53 have received accelerated approval in the USA. In preclinical setting, the <jats:italic>mdx<\/jats:italic> mouse model, carrying a point mutation in exon 23 of the murine <jats:italic>Dmd<\/jats:italic> gene that prevents production of dystrophin protein, has emerged as a valuable tool, and it is widely used to study in vivo therapeutic approaches for DMD. Here we describe the methodology for intravenous delivery of AONs targeting dystrophin through tail vein of <jats:italic>mdx<\/jats:italic> mice. Furthermore, the most relevant functional analyses to be performed in living mice, and the most informative histopathological and molecular assays to evaluate the effect of this treatment are detailed.<\/jats:p>","DOI":"10.1007\/978-1-0716-2010-6_20","type":"book-chapter","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T11:11:35Z","timestamp":1645787495000},"page":"301-313","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Use of Small Animal Models for Duchenne and Parameters to Assess Efficiency upon Antisense Treatment"],"prefix":"10.1007","author":[{"given":"Ngoc","family":"Lu-Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Malerba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Popplewell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"issue":"3","key":"20_CR1","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/0092-8674(87)90504-6","volume":"50","author":"M Koenig","year":"1987","unstructured":"Koenig M, Hoffman EP, Bertelson CJ et al (1987) Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. 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Biochem Soc Trans 24(2):276S","journal-title":"Biochem Soc Trans"},{"issue":"2","key":"20_CR4","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/mt.2010.261","volume":"19","author":"A Malerba","year":"2011","unstructured":"Malerba A, Sharp PS, Graham IR et al (2011) Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx mice. Mol Ther 19(2):345\u2013354","journal-title":"Mol Ther"},{"key":"20_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2012.54","volume":"1","author":"A Malerba","year":"2012","unstructured":"Malerba A, Kang JK, McClorey G et al (2012) Dual myostatin and dystrophin exon skipping by morpholino nucleic acid oligomers conjugated to a cell-penetrating peptide is a promising therapeutic strategy for the treatment of Duchenne muscular dystrophy. Mol Ther Nucleic Acids 1:e62. https:\/\/doi.org\/10.1038\/mtna.2012.54","journal-title":"Mol Ther Nucleic Acids"},{"issue":"8","key":"20_CR6","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/mt.2015.88","volume":"23","author":"NB Lu-Nguyen","year":"2015","unstructured":"Lu-Nguyen NB, Jarmin SA, Saleh AF et al (2015) Combination antisense treatment for destructive exon skipping of myostatin and open reading frame rescue of dystrophin in neonatal mdx mice. Mol Ther 23(8):1341\u20131348","journal-title":"Mol Ther"},{"key":"20_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.omtn.2016.11.009","volume":"6","author":"N Lu-Nguyen","year":"2017","unstructured":"Lu-Nguyen N, Malerba A, Popplewell L et al (2017) Systemic antisense therapeutics for dystrophin and myostatin exon splice modulation improve muscle pathology of adult mdx mice. 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Hum Mol Genet 28(18):3091\u20133100","journal-title":"Hum Mol Genet"}],"container-title":["Methods in Molecular Biology","Antisense RNA Design, Delivery, and Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/978-1-0716-2010-6_20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:33:05Z","timestamp":1650587585000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/978-1-0716-2010-6_20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"ISBN":["9781071620090","9781071620106"],"references-count":8,"URL":"https:\/\/doi.org\/10.1007\/978-1-0716-2010-6_20","relation":{},"ISSN":["1064-3745","1940-6029"],"issn-type":[{"value":"1064-3745","type":"print"},{"value":"1940-6029","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]},"assertion":[{"value":"25 February 2022","order":1,"name":"first_online","label":"First Online","group":{"name":"ChapterHistory","label":"Chapter History"}}]}}