{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:42:02Z","timestamp":1785825722775,"version":"3.56.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lee and Penny Anderson Family Foundation"},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cure ADSSL1 Foundation"},{"name":"Rich Horgan and Cure Rare Disease"},{"name":"Boston Children\u2019s Hospital Intellectual and Developmental Disabilities Research Center Molecular Genetics Core Facility","award":["P50HD105351"],"award-info":[{"award-number":["P50HD105351"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development of NIH"},{"name":"Harvard College Research Program"},{"name":"Boston Children\u2019s Hospital Developmental Neurology Training","award":["T32NS007473"],"award-info":[{"award-number":["T32NS007473"]}]},{"name":"National Institute of Neurological Disorders and Stroke of NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>ADSS1 myopathy is an ultrarare congenital myopathy characterized by progressive cardiac and skeletal muscle degeneration with childhood to adolescent onset. This autosomal recessive disease is caused by mutations in the ADSS1 gene, encoding the enzyme adenylosuccinate synthetase (AdSS1). AdSS1 plays a critical role in the adenine nucleotide cycle, which is important for energy metabolism in muscle cells. Enzymatic defects, engendered by loss-of-function mutations in ADSS1, lead to a bottleneck in the adenine nucleotide cycle, causing metabolic dysfunction that ultimately results in progressive muscle weakness, mobility impairment, and respiratory and cardiac dysfunction, often requiring the use of a ventilator. Despite its debilitating nature, there are currently no cures or targeted treatments available, and little research into possible therapeutic strategies has been done. With a limited patient profile encompassing fewer than 200 known patients worldwide, establishing a mouse model for ADSS1 myopathy is critical to understanding its pathogenesis and for developing future therapies. Here, we present and characterize the first mouse model of ADSS1 myopathy\u2014a constitutive Adss1 knockout model\u2014by (1) defining its natural history, (2) exploring its metabolic pathomechanisms, and (3) characterizing its histopathological features. We find that Adss1KO\/KO mice have subtle motor deficits and present with histopathological features consistent with patient phenotypes. Overall, we show that despite a relatively mild phenotype, this novel mouse model has quantifiable pathological features that can be used to develop therapies for, and further probe pathophysiology of, ADSS1 myopathy.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf167","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:12:19Z","timestamp":1763651539000},"source":"Crossref","is-referenced-by-count":3,"title":["Loss of adenylosuccinate synthetase 1 in mice recapitulates features of\n                    <i>ADSS1<\/i>\n                    myopathy"],"prefix":"10.1093","volume":"35","author":[{"given":"Morgan E","family":"Kim","sequence":"first","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M","family":"Yammine","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily T","family":"Hickey","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Matias","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine , 635 Barnhill Drive, Indianapolis, IN, 46202 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lou C","family":"Dubosclard","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]},{"name":"Faculty of Science & Engineering, Sorbonne Universit\u00e9 , 21 Rue de l\u2019\u00c9cole de M\u00e9decine, 75006 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J","family":"Widrick","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J","family":"Brault","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health, Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine , 635 Barnhill Drive, Indianapolis, IN, 46202 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Moghadaszadeh","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8818-0568","authenticated-orcid":false,"given":"Alan H","family":"Beggs","sequence":"additional","affiliation":[{"name":"The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School , 3 Blackfan St., Boston, MA, 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2026051101323385300_ref1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/ana.24550","article-title":"ADSSL1 mutation relevant to autosomal recessive adolescent onset distal myopathy","volume":"79","author":"Park","year":"2016","journal-title":"Ann Neurol"},{"key":"2026051101323385300_ref2","doi-asserted-by":"publisher","first-page":"e1500","DOI":"10.1212\/WNL.0000000000010237","article-title":"ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features","volume":"95","author":"Saito","year":"2020","journal-title":"Neurology"},{"key":"2026051101323385300_ref3","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s13023-024-03429-x","article-title":"Current insights in ultra-rare adenylosuccinate synthetase 1 myopathy - 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