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Resistance to thyro...
Resistance to thyroid hormone induced tachycardia in RTHα syndrome
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- Dore, Riccardo (author)
- British Columbia Children's Hospital
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- Watson, Laura (author)
- Addenbrooke's Hospital
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- Hollidge, Stefanie (author)
- University of Cambridge
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- Krause, Christin (author)
- British Columbia Children's Hospital
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- Sentis, Sarah Christine (author)
- British Columbia Children's Hospital
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- Oelkrug, Rebecca (author)
- British Columbia Children's Hospital
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- Geißler, Cathleen (author)
- British Columbia Children's Hospital
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- Johann, Kornelia (author)
- British Columbia Children's Hospital
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- Pedaran, Mehdi (author)
- British Columbia Children's Hospital
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- Lyons, Greta (author)
- University of Cambridge
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- Lopez-Alcantara, Nuria (author)
- British Columbia Children's Hospital
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- Resch, Julia (author)
- British Columbia Children's Hospital
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- Sayk, Friedhelm (author)
- University Medical Center Schleswig-Holstein
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- Iwen, Karl Alexander (author)
- British Columbia Children's Hospital,University Medical Center Schleswig-Holstein
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- Franke, Andre (author)
- University of Kiel
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- Boysen, Teide Jens (author)
- University of Kiel
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- Dalley, Jeffrey W. (author)
- University of Cambridge
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- Lorenz, Kristina (author)
- Leibniz Institute For Analytical Sciences (ISAS),Julius Maximilian University of Würzburg
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- Moran, Carla (author)
- University College Dublin,University of Cambridge
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- Rennie, Kirsten L. (author)
- University of Cambridge
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- Arner, Anders (author)
- Lund University,Lunds universitet,Thoraxkirurgi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Thoracic Surgery,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Igelösa Life Science AB
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- Kirchner, Henriette (author)
- British Columbia Children's Hospital
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- Chatterjee, Krishna (author)
- University of Cambridge
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- Mittag, Jens (author)
- British Columbia Children's Hospital
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Nature Communications. - 2041-1723. ; 14:1
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Dore, Riccardo
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Watson, Laura
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Hollidge, Stefan ...
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Krause, Christin
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Sentis, Sarah Ch ...
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Oelkrug, Rebecca
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show more...
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Geißler, Cathlee ...
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Johann, Kornelia
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Pedaran, Mehdi
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Lyons, Greta
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Lopez-Alcantara, ...
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Resch, Julia
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Sayk, Friedhelm
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Iwen, Karl Alexa ...
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Franke, Andre
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Boysen, Teide Je ...
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Dalley, Jeffrey ...
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Lorenz, Kristina
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Moran, Carla
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Rennie, Kirsten ...
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Arner, Anders
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Kirchner, Henrie ...
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Chatterjee, Kris ...
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Mittag, Jens
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University