{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:58:46Z","timestamp":1785927526508,"version":"3.56.0"},"reference-count":30,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,20]]},"abstract":"<jats:p>Nexilin (NEXN) was recently identified as a component of the junctional membrane complex required for development and maintenance of cardiac T-tubules. Loss of Nexn in mice leads to a rapidly progressive dilated cardiomyopathy (DCM) and premature death. A 3 bp deletion (1948\u20131950del) leading to loss of the glycine in position 650 (G650del) is classified as a variant of uncertain significance in humans and may function as an intermediate risk allele. To determine the effect of the G650del variant on cardiac structure and function, we generated a G645del-knockin (G645del is equivalent to human G650del) mouse model. Homozygous G645del mice express about 30% of the Nexn expressed by WT controls and exhibited a progressive DCM characterized by reduced T-tubule formation, with disorganization of the transverse-axial tubular system. On the other hand, heterozygous Nexn global KO mice and genetically engineered mice encoding a truncated Nexn missing the first N-terminal actin-binding domain exhibited normal cardiac function, despite expressing only 50% and 20% of the Nexn, respectively, expressed by WT controls, suggesting that not only quantity but also quality of Nexn is necessary for a proper function. These findings demonstrated that Nexn G645 is crucial for Nexn\u2019s function in tubular system organization and normal cardiac function.<\/jats:p>","DOI":"10.1172\/jci.insight.138780","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T11:01:22Z","timestamp":1597834882000},"source":"Crossref","is-referenced-by-count":17,"title":["Homozygous G650del nexilin variant causes cardiomyopathy in mice"],"prefix":"10.1172","volume":"5","author":[{"given":"Canzhao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medicine, UCSD, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Spinozzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, UCSD, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medicine, UCSD, La Jolla, California, 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