{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:36:51Z","timestamp":1791283011237,"version":"4.1.0"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:italic>Sorbs2b<\/jats:italic>\n              (sorbin and SH3 domain\u2010containing 2b) was recently identified as a cardiomyopathy gene from a zebrafish mutagenesis screen. However, cardiac functions of its mammalian ortholog remain elusive.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We conducted a detailed expression and subcellular localization analysis of Sorbs2 ortholog in mice and a phenotypic characterization in Sorbs2 knockout mice.\n              <jats:italic>Sorbs2<\/jats:italic>\n              is highly expressed in the mouse heart and encodes an adhesion junction\/desmosome protein that is mainly localized to the intercalated disc. A mutation with near complete depletion of the Sorbs2 protein in mice results in phenotypes characteristic of human arrhythmogenic cardiomyopathy (ACM), including right ventricular dilation, right ventricular dysfunction, spontaneous ventricular tachycardia, and premature death. Sorbs2 is required to maintain the structural integrity of intercalated disc. Its absence resulted in profound cardiac electrical remodeling with impaired impulse conduction and action potential derangements. Targeted sequencing of human patients with ACM identified 2 rare splicing variants classified as likely pathogenic were in 2 unrelated individuals with ACM from a cohort of 59 patients with ACM.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The Sorbs2 knockout mouse manifests several key features reminiscent of human ACM. Although the candidacy of\n              <jats:italic>SORBS2<\/jats:italic>\n              as a new ACM\u2010susceptibility gene is supported by preliminary human genetics study, future validation in larger cohorts with ACM is needed.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.017055","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T09:04:45Z","timestamp":1597741485000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Knockout of SORBS2 Protein Disrupts the Structural Integrity of Intercalated Disc and Manifests Features of Arrhythmogenic Cardiomyopathy"],"prefix":"10.1161","volume":"9","author":[{"given":"Yonghe","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic Rochester MN"},{"name":"Department of Cardiovascular Medicine Mayo Clinic Rochester 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