{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:46:33Z","timestamp":1790757993287,"version":"4.1.0"},"reference-count":37,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":497,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007423","name":"Duchenne Parent Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>For many genetic diseases, researchers are developing personalized medicine approaches. These sometimes employ custom genetic interventions such as antisense-mediated exon skipping or genome editing, aiming to restore protein function in a mutation-specific manner. Animal models can facilitate the development of personalized medicine approaches; however, given that they target human mutations and therefore human genetic sequences, scientists rely on the availability of humanized animal models. Here, we outline the usefulness, caveats and potential of such models, using the example of the hDMDdel52\/mdx model, a humanized model recently generated for Duchenne muscular dystrophy (DMD).<\/jats:p>","DOI":"10.1242\/dmm.041673","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T14:34:11Z","timestamp":1569940451000},"source":"Crossref","is-referenced-by-count":28,"title":["The use of genetically humanized animal models for personalized medicine approaches"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1565-654X","authenticated-orcid":false,"given":"Annemieke","family":"Aartsma-Rus","sequence":"first","affiliation":[{"name":"Leiden University Medical Center Department of Human Genetics , , Albinusdreef 2, 2333 ZA Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"van Putten","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Department of Human Genetics , , Albinusdreef 2, 2333 ZA Leiden , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"2024061010065140100_DMM041673C1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/nat.2016.0657","article-title":"FDA approves eteplirsen for duchenne muscular dystrophy: the next chapter in the Eteplirsen Saga","volume":"27","author":"Aartsma-Rus","year":"2017","journal-title":"Nucleic Acid Ther."},{"key":"2024061010065140100_DMM041673C2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/mus.20586","article-title":"Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule","volume":"34","author":"Aartsma-Rus","year":"2006","journal-title":"Muscle Nerve"},{"key":"2024061010065140100_DMM041673C3","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/mt.2008.205","article-title":"Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms","volume":"17","author":"Aartsma-Rus","year":"2009","journal-title":"Mol. Ther."},{"key":"2024061010065140100_DMM041673C4","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1089\/hum.2006.061","article-title":"Comparative analysis of antisense oligonucleotide sequences for targeted skipping of exon 51 during dystrophin pre-mRNA splicing in human muscle","volume":"18","author":"Arechavala-Gomeza","year":"2007","journal-title":"Hum. Gene. Ther."},{"key":"2024061010065140100_DMM041673C5","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/S1474-4422(18)30025-5","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"2024061010065140100_DMM041673C6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S1474-4422(18)30024-3","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"2024061010065140100_DMM041673C7","doi-asserted-by":"publisher","first-page":"e10486","DOI":"10.15252\/emmm.201910486","article-title":"International collaborative actions and transparency to understand, diagnose, and develop therapies for rare diseases","volume":"11","author":"Boycott","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"2024061010065140100_DMM041673C8","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.ymthe.2004.05.031","article-title":"Targeted exon skipping in transgenic hDMD mice: A model for direct preclinical screening of human-specific antisense oligonucleotides","volume":"10","author":"Bremmer-Bout","year":"2004","journal-title":"Mol. Ther."},{"key":"2024061010065140100_DMM041673C9","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1093\/hmg\/ddv460","article-title":"Effect of genetic background on the dystrophic phenotype in mdx mice","volume":"25","author":"Coley","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2024061010065140100_DMM041673C10","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1089\/hum.2016.079","article-title":"Duchenne muscular dystrophy myogenic cells from urine-derived stem cells recapitulate the dystrophin genotype and phenotype","volume":"27","author":"Falzarano","year":"2016","journal-title":"Hum. Gene. Ther."},{"key":"2024061010065140100_DMM041673C11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/14712598.2017.1250880","article-title":"Translational development of splice-modifying antisense oligomers","volume":"17","author":"Fletcher","year":"2017","journal-title":"Expert Opin Biol. Ther."},{"key":"2024061010065140100_DMM041673C12","doi-asserted-by":"publisher","first-page":"e79369","DOI":"10.1371\/journal.pone.0079369","article-title":"Unexpected CEP290 mRNA splicing in a humanized knock-in mouse model for Leber congenital amaurosis","volume":"8","author":"Garanto","year":"2013","journal-title":"PLoS ONE"},{"key":"2024061010065140100_DMM041673C13","doi-asserted-by":"publisher","first-page":"5285","DOI":"10.3390\/ijms16035285","article-title":"Species-dependent splice recognition of a cryptic exon resulting from a recurrent intronic CEP290 mutation that causes congenital blindness","volume":"16","author":"Garanto","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"2024061010065140100_DMM041673C14","doi-asserted-by":"publisher","first-page":"407","DOI":"10.3233\/JND-180324","article-title":"\u201cOf Mice and Measures\u201d: a project to improve how we advance duchenne muscular dystrophy therapies to the clinic","volume":"5","author":"Gordish-Dressman","year":"2018","journal-title":"J. Neuromuscul. Dis."},{"key":"2024061010065140100_DMM041673C15","doi-asserted-by":"publisher","first-page":"124297","DOI":"10.1172\/jci.insight.124297","article-title":"AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice","volume":"3","author":"Hakim","year":"2018","journal-title":"JCI Insight"},{"key":"2024061010065140100_DMM041673C16","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1002\/jgm.1288","article-title":"In vivo comparison of 2\u2032-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping","volume":"11","author":"Heemskerk","year":"2009","journal-title":"J. Gene Med."},{"key":"2024061010065140100_DMM041673C17","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.nmd.2005.05.004","article-title":"Genetic background influences muscular dystrophy","volume":"15","author":"Heydemann","year":"2005","journal-title":"Neuromuscul. Disord."},{"key":"2024061010065140100_DMM041673C18","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0092-8674(88)90383-2","article-title":"The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein","volume":"53","author":"Koenig","year":"1988","journal-title":"Cell"},{"key":"2024061010065140100_DMM041673C19","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/s41431-018-0115-5","article-title":"RD-Connect, NeurOmics and EURenOmics: collaborative European initiative for rare diseases","volume":"26","author":"Lochm\u00fcller","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"2024061010065140100_DMM041673C20","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1126\/science.aad5725","article-title":"Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy","volume":"351","author":"Long","year":"2016","journal-title":"Science"},{"key":"2024061010065140100_DMM041673C21","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/nm897","article-title":"Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse","volume":"9","author":"Lu","year":"2003","journal-title":"Nat. Med."},{"key":"2024061010065140100_DMM041673C22","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1002\/jgm.295","article-title":"Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophy","volume":"4","author":"Mann","year":"2002","journal-title":"J. Gene Med."},{"key":"2024061010065140100_DMM041673C23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1242\/dmm.018424","article-title":"Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy","volume":"8","author":"Mcgreevy","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"2024061010065140100_DMM041673C24","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/0888-7543(88)90113-9","article-title":"An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus","volume":"2","author":"Monaco","year":"1988","journal-title":"Genomics"},{"key":"2024061010065140100_DMM041673C25","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1126\/science.aad5143","article-title":"In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy","volume":"351","author":"Nelson","year":"2016","journal-title":"Science"},{"key":"2024061010065140100_DMM041673C26","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.nmd.2009.10.013","article-title":"Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of the human DMD gene: implications for future clinical trials","volume":"20","author":"Popplewell","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"2024061010065140100_DMM041673C27","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1126\/science.2662404","article-title":"The molecular basis of muscular dystrophy in the mdx mouse: a point mutation","volume":"244","author":"Sicinski","year":"1989","journal-title":"Science"},{"key":"2024061010065140100_DMM041673C28","doi-asserted-by":"publisher","first-page":"5899","DOI":"10.1074\/jbc.M709410200","article-title":"Generation and characterization of transgenic mice with the full-length human DMD gene","volume":"283","author":"'t Hoen","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2024061010065140100_DMM041673C29","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1126\/science.aad5177","article-title":"In vivo gene editing in dystrophic mouse muscle and muscle stem cells","volume":"351","author":"Tabebordbar","year":"2016","journal-title":"Science"},{"key":"2024061010065140100_DMM041673C30","doi-asserted-by":"publisher","first-page":"8110","DOI":"10.1096\/fj.201802488R","article-title":"Natural disease history of the D2-mdx mouse model for Duchenne muscular dystrophy","volume":"33","author":"van Putten","year":"2019","journal-title":"FASEB J."},{"key":"2024061010065140100_DMM041673C31","doi-asserted-by":"publisher","DOI":"10.1371\/currents.md.cbf1d33001de80923ce674302cad7925","article-title":"Generation of embryonic stem cells and mice for duchenne research","volume":"5","author":"Veltrop","year":"2013","journal-title":"PLoS Curr."},{"key":"2024061010065140100_DMM041673C32","doi-asserted-by":"publisher","first-page":"e0193289","DOI":"10.1371\/journal.pone.0193289","article-title":"A dystrophic Duchenne mouse model for testing human antisense oligonucleotides","volume":"13","author":"Veltrop","year":"2018","journal-title":"PLoS ONE"},{"key":"2024061010065140100_DMM041673C33","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/s41582-019-0203-3","article-title":"Therapeutic developments for Duchenne muscular dystrophy","volume":"15","author":"Verhaart","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"2024061010065140100_DMM041673C34","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.nmd.2019.06.004","article-title":"Muscle biopsies in clinical trials for Duchenne muscular dystrophy - Patients\u2019 and caregivers\u2019 perspective","volume":"29","author":"Verhaart","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"2024061010065140100_DMM041673C35","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/S0960-8966(99)00010-3","article-title":"Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides","volume":"9","author":"Wilton","year":"1999","journal-title":"Neuromuscul. Disord."},{"key":"2024061010065140100_DMM041673C36","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1038\/sj.mt.6300095","article-title":"Antisense oligonucleotide-induced exon skipping across the human dystrophin gene transcript","volume":"15","author":"Wilton","year":"2007","journal-title":"Mol. Ther."},{"key":"2024061010065140100_DMM041673C37","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3233\/JND-170218","article-title":"Creation of a novel humanized dystrophic mouse model of Duchenne muscular dystrophy and application of a CRISPR\/Cas9 gene editing therapy","volume":"4","author":"Young","year":"2017","journal-title":"J. Neuromuscul. Dis."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.041673","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.041673\/3442063\/dmm041673.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.041673\/3442063\/dmm041673.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T10:10:54Z","timestamp":1718014254000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/13\/2\/dmm041673\/225280\/The-use-of-genetically-humanized-animal-models-for"}},"subtitle":[],"editor":[{"given":"Annemieke","family":"Aartsma-Rus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"James","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Maaike","family":"van Putten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.041673","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10,1]]},"article-number":"dmm041673"}}