{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:20:13Z","timestamp":1793089213398,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2020,4,10]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>\n                      Barth syndrome is an X-linked cardiac and skeletal myopathy caused by mutation of the gene Tafazzin (\n                      <jats:italic>TAZ<\/jats:italic>\n                      ). Currently, there is no targeted treatment for Barth syndrome. Lack of a proper genetic animal model that recapitulates the features of Barth syndrome has hindered understanding of disease pathogenesis and therapeutic development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      We characterized murine germline\n                      <jats:italic>TAZ<\/jats:italic>\n                      knockout mice (TAZ-KO) and cardiomyocyte-specific\n                      <jats:italic>TAZ<\/jats:italic>\n                      knockout mice models and tested the efficacy of adeno-associated virus (AAV)-mediated gene replacement therapy with human\n                      <jats:italic>TAZ<\/jats:italic>\n                      (hTAZ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      TAZ-KO caused embryonic and neonatal lethality, impaired growth, dilated cardiomyopathy, and skeletal myopathy. TAZ-KO mice that survived the neonatal period developed progressive, severe cardiac dysfunction, and fibrosis. Cardiomyocyte-specific inactivation of floxed\n                      <jats:italic>Taz<\/jats:italic>\n                      in cardiomyocytes using\n                      <jats:italic>Myh6-Cre<\/jats:italic>\n                      caused progressive dilated cardiomyopathy without fetal or perinatal loss. Using both constitutive and conditional knockout models, we tested the efficacy and durability of\n                      <jats:italic>Taz<\/jats:italic>\n                      replacement by\n                      <jats:italic>AAV<\/jats:italic>\n                      gene therapy. Neonatal AAV-hTAZ rescued neonatal death, cardiac dysfunction, and fibrosis in TAZ-KO mice, and both prevented and reversed established cardiac dysfunction in TAZ-KO and cardiomyocyte-specific\n                      <jats:italic>TAZ<\/jats:italic>\n                      knockout mice models. However, both neonatal and adult therapies required high cardiomyocyte transduction (\u224870%) for durable efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      TAZ-KO and cardiomyocyte-specific\n                      <jats:italic>TAZ<\/jats:italic>\n                      knockout mice recapitulate many of the key clinical features of Barth syndrome. AAV-mediated gene replacement is efficacious when a sufficient fraction of cardiomyocytes are transduced.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.119.315956","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T14:32:12Z","timestamp":1584541932000},"page":"1024-1039","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":126,"title":["AAV Gene Therapy Prevents and Reverses Heart Failure in a Murine Knockout Model of Barth Syndrome"],"prefix":"10.1161","volume":"126","author":[{"given":"Suya","family":"Wang","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, MA (S.W., Y.L., Q.M., Z.L., V.J.B., W.T.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, MA (S.W., Y.L., Q.M., Z.L., V.J.B., W.T.P.)"},{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China (Y.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China (Y.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, MA (S.W., Y.L., Q.M., Z.L., V.J.B., W.T.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Lin","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, MA (S.W., Y.L., Q.M., Z.L., V.J.B., W.T.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schlame","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology (Y.X., M.S.)"},{"name":"Department of Cell Biology (M.S.), New York University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios J.","family":"Bezzerides","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, MA (S.W., Y.L., Q.M., Z.L., V.J.B., W.T.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Strathdee","sequence":"additional","affiliation":[{"name":"Transgenic Technology Laboratory, Cancer Research UK Beatson Institute, Glasgow, United Kingdom (D.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4551-8079","authenticated-orcid":false,"given":"William T.","family":"Pu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, MA (S.W., Y.L., Q.M., Z.L., V.J.B., W.T.P.)"},{"name":"Harvard Stem Cell Institute, Harvard University, Cambridge, MA 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