{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:26:58Z","timestamp":1791563218418,"version":"4.3.4"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:p>\n                    The sodium-dependent multivitamin transporter, encoded by\n                    <jats:italic>SLC5A6<\/jats:italic>\n                    , mediates cellular uptake of biotin and pantothenic acid, essential cofactors for energy metabolism. We identified 2 families with\n                    <jats:italic>SLC5A6<\/jats:italic>\n                    mutations presenting with early-onset dilated cardiomyopathy (DCM). To investigate the link between vitamin deficiency and cardiomyopathy, we generated a cardiac-specific\n                    <jats:italic>SLC5A6<\/jats:italic>\n                    -knockout (\n                    <jats:italic>\n                      Slc5a6\n                      <jats:sup>cKO<\/jats:sup>\n                    <\/jats:italic>\n                    ) mouse model and evaluated the impact of vitamin supplementation.\n                    <jats:italic>\n                      Slc5a6\n                      <jats:sup>cKO<\/jats:sup>\n                    <\/jats:italic>\n                    mice developed progressive cardiac dysfunction, culminating in cardiac pathology and premature death at 26 weeks; earlier stages exhibited cardiomyocyte hypertrophy, fibrosis, impaired coenzyme A synthesis, and metabolic imbalance, indicating progression toward cardiomyopathy. Cardiac magnetic resonance imaging and ECG confirmed progressive functional decline. Proteomic analysis revealed early mitochondrial metabolic disruption and extracellular matrix protein upregulation at 8 weeks, preceding overt cardiac dysfunction. Strikingly, vitamin supplementation from preconception onwards prevented the cardiac phenotype, preserving cardiac structure, function, morphology and survival. This paralleled the clinical outcome in one patient who received early vitamin treatment, compared with another who required a heart transplant without vitamin treatment. This study establishes a direct link between\n                    <jats:italic>SLC5A6<\/jats:italic>\n                    -mediated vitamin transport, mitochondrial function, and cardiac health. It highlights how vitamin deficiency contributes to cardiomyopathy pathogenesis and supports early vitamin supplementation as a potential therapeutic strategy for metabolic cardiomyopathies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.200381","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:01:06Z","timestamp":1780416066000},"source":"Crossref","is-referenced-by-count":1,"title":["A Slc5a6-deficient mouse model reveals metabolically driven cardiomyopathy with therapeutic potential for vitamin-based intervention"],"prefix":"10.1172","volume":"11","author":[{"given":"Millie O.","family":"Fullerton","sequence":"first","affiliation":[{"name":"Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University, Newcastle upon Tyne, United 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