{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T14:46:47Z","timestamp":1748530007438,"version":"3.38.0"},"reference-count":25,"publisher":"American Veterinary Medical Association (AVMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To compare mitochondrial oxygen consumption rate (OCR) of fibroblasts from Doberman Pinschers with and without dilated cardiomyopathy (DCM) and mutation of the gene for pyruvate dehydrogenase kinase isozyme 4 (<jats:italic>PDK4<\/jats:italic>) and to evaluate in vitro whether treatment with adeno-associated virus (AAV) vector (ie, gene therapy) would alter metabolic efficiency.<\/jats:p>\n<jats:p><jats:bold>ANIMALS<\/jats:bold> 10 Doberman Pinschers screened for DCM and <jats:italic>PDK4<\/jats:italic> mutation.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Fibroblasts were harvested from skin biopsy specimens obtained from Doberman Pinschers, and dogs were classified as without DCM or <jats:italic>PDK4<\/jats:italic> mutation (n = 3) or with occult DCM and heterozygous (4) or homozygous (3) for <jats:italic>PDK4<\/jats:italic> mutation. Fibroblasts were or were not treated with tyrosine mutant AAV type 2 vector containing <jats:italic>PDK4<\/jats:italic> at multiplicities of infection of 1,000. Mitochondrial OCR was measured to evaluate mitochondrial metabolism. The OCR was compared among dog groups and between untreated and treated fibroblasts within groups.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> Mean \u00b1 SD basal OCR of fibroblasts from heterozygous (74 \u00b1 8 pmol of O<jats:sub>2<\/jats:sub>\/min) and homozygous (58 \u00b1 12 pmol of O<jats:sub>2<\/jats:sub>\/min) dogs was significantly lower than that for dogs without <jats:italic>PDK4<\/jats:italic> mutation (115 \u00b1 9 pmol of O<jats:sub>2<\/jats:sub>\/min). After AAV transduction, OCR did not increase significantly in any group (mutation-free group, 121 \u00b1 26 pmol of O<jats:sub>2<\/jats:sub>\/min; heterozygous group, 88 \u00b1 6 pmol of O<jats:sub>2<\/jats:sub>\/min; homozygous group, 59 \u00b1 3 pmol of O<jats:sub>2<\/jats:sub>\/min).<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> Mitochondrial function was altered in skin fibroblasts of Doberman Pinschers with DCM and <jats:italic>PDK4<\/jats:italic> mutation. Change in mitochondrial function after in vitro gene therapy at the multiplicities of infection used in this study was not significant. 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