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Pathogenic GAA variants result in enzyme dysfunction and glycogen storage in cardiac, skeletal and smooth muscle, as well as in the central nervous system, driving both systemic and neurological manifestations. We have previously characterized a transgenic knock-in (KI) mouse carrying the Gaa c.1826dupA variant to 12\u2005weeks of age, showing that it recapitulates key biochemical and phenotypic features of PD. Here, we extend this analysis to present a long-term characterization of this Gaa c.1826dupA KI mouse model by using physiological, behavioral, biochemical and histopathological assessments. KI mice exhibited early-onset hypertrophic cardiomyopathy with significant cardiac functional decline, reduced body mass, impaired skeletal muscle strength, locomotion, coordination and balance. Biochemically, KI mice showed decreased GAA activity and increased lysosomal glycogen accumulation in the heart, diaphragm, gastrocnemius and brain. Despite these abnormalities, survival did not differ from wild-type mice \u2013 a divergence from severe human PD but consistent with other murine models. Collectively, these findings support this KI model as a translational platform for therapeutic evaluation in PD.<\/jats:p>","DOI":"10.1242\/dmm.052611","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T08:09:36Z","timestamp":1770019776000},"source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal characterization of\n                    <i>Gaa<\/i>\n                    c.1826dupA mice reveals the cardiac, myopathic and biochemical phenotypes of Pompe disease"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5457-6564","authenticated-orcid":false,"given":"Jerry F.","family":"Harb","sequence":"first","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]},{"name":"University of California-Irvine School of Medicine 2 Department of Pediatrics , , Irvine, CA 92697 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-4963","authenticated-orcid":false,"given":"Shih-hsin","family":"Kan","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]},{"name":"University of California-Irvine School of Medicine 2 Department of Pediatrics , , Irvine, CA 92697 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe L.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]},{"name":"University of California-Irvine School of Medicine 2 Department of Pediatrics , , Irvine, CA 92697 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allisandra K.","family":"Rha","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perla","family":"Andrade-Heckman","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agatha","family":"Kliman","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Padilla","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Loma Linda University Children's Health 3 Pediatric Cardiac Lab , , Loma Linda, CA 92354 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey Y.","family":"Huang","sequence":"additional","affiliation":[{"name":"Research Institute, Children's Hospital of Orange County 1 , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-2464","authenticated-orcid":false,"given":"Dwight D.","family":"Koeberl","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine 4 Department of Pediatrics , , Durham, NC 27710 ,","place":["USA"]},{"name":"Duke University Medical Center 5 Department of Molecular Genetics and Microbiology , , Durham, NC 27710 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-7613","authenticated-orcid":false,"given":"Raymond Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"University of California-Irvine School of Medicine 2 Department of Pediatrics , , Irvine, CA 92697 ,","place":["USA"]},{"name":"Children's Hospital of Orange County Specialists 6 Division of Metabolic Disorders , , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026031807563031200_DMM052611C1","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1097\/00125817-200103000-00008","article-title":"Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I\/II clinical trial","volume":"3","author":"Amalfitano","year":"2001","journal-title":"Genet. 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