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Zebrafish larvae as...
Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
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- Bandaru, Manoj Kumar (author)
- Uppsala universitet,Medicinsk genetik och genomik
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- Emmanouilidou, Anastasia (author)
- Uppsala universitet,Medicinsk genetik och genomik
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Ranefall, Petter (author)
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- von der Heyde, Benedikt (author)
- Uppsala universitet,Medicinsk genetik och genomik
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- Mazzaferro, Eugenia (author)
- Uppsala universitet,Medicinsk genetik och genomik
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Klingström, Tiffany (author)
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Masiero, Mauro (author)
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Dethlefsen, Olga (author)
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Ledin, Johan (author)
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Larsson, Anders (author)
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Brooke, Hannah (author)
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Wählby, Carolina (author)
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Ingelsson, Erik (author)
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- den Hoed, Marcel (author)
- Uppsala universitet,Medicinsk genetik och genomik
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
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- Background: Hundreds of loci have been robustly associated with circulating lipids, atherosclerosis and coronary artery disease; but for most loci the causal genes and mechanisms remain uncharacterized.Methods: We developed a semi-automated experimental pipeline for systematic, quantitative, large-scale characterization of mechanisms, drugs and genes associated with dyslipidemia and atherosclerosis in a zebrafish model system. We validated our pipeline using a dietary (n>2000), drug treatment (n>1000), and genetic intervention (n=384).Results: Our results show that five days of overfeeding and cholesterol supplementation had independent pro-atherogenic effects, which could be diminished by concomitant treatment with atorvastatin and ezetimibe. CRISPR-Cas9-induced mutations in orthologues of proof-of-concept genes resulted in higher LDL cholesterol levels (apoea), and more early stage atherosclerosis (apobb.1).Conclusions: In summary, our pipeline facilitates systematic, in vivo characterization of drugs and candidate genes to increase our understanding of disease etiology, and can likely help identify novel targets for therapeutic intervention.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bandaru, Manoj K ...
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Emmanouilidou, A ...
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Ranefall, Petter
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von der Heyde, B ...
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Mazzaferro, Euge ...
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Klingström, Tiff ...
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show more...
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Masiero, Mauro
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Dethlefsen, Olga
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Ledin, Johan
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Larsson, Anders
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Brooke, Hannah
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Wählby, Carolina
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Ingelsson, Erik
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den Hoed, Marcel
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- By the university
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Uppsala University