dc.description.abstract |
Calcification of various tissues is a significant health issue associated with aging, cancer and autoimmune diseases. There are both environmental and genetic factors behind this phenomenon and understanding them is essential for the development of efficient therapeutic approaches. Pseudoxanthoma elasticum (PXE) is a rare genetic disease, a prototype for calcification disorders, resulting from the dysfunction of ABCC6, a transport protein found in the membranes of cells. It is identified by excess calcification in a variety of tissues (e.g., eyes, skin, arteries) and currently it has no cure, known treatments target the symptoms only. Preclinical studies of PXE have been successful in mice, proving the usefulness of animal models for the study of the disease. Here, we present a new zebrafish (Danio rerio) model for PXE. By resolving some ambiguous assemblies in the zebrafish genome, we show that there are two functional and one non-functional paralogs for ABCC6 in zebrafish (abcc6a, abcc6b.1, and abcc6b.2, respectively). We created single and double mutants for the functional paralogs and characterized their calcification defects with a combination of techniques. Zebrafish deficient in abcc6a show defects in their vertebral calcification and also display ectopic calcification foci in their soft tissues. Our results also suggest that the impairment of abcc6b.1 does not affect this biological process. |
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dc.mtmt.swordnote |
Department of Genetics, ELTE Eötvös Loránd University, Budapest, Hungary
Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Division of Biosciences, University College London, London, United Kingdom
Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China
Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, United States
Export Date: 7 April 2021
Correspondence Address: Varga, M.; Department of Genetics, Hungary; email: mvarga@ttk.elte.hu
Correspondence Address: Váradi, A.; Institute of Enzymology, Hungary; email: varadi.andras@ttk.hu
Funding details: National Institutes of Health, NIH, 1ZIAHG000183-20
Funding details: National Human Genome Research Institute, NHGRI
Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K-125977, NKFIH K-119287, NKFIH K-119653, NKFIH UK_GYAK-2018-00004, NN-127933, NVKP_16-2016-1-0039
Funding details: National Research, Development and Innovation Office, R01AR072695, TKP2020-IKA-05
Funding text 1: This work was funded by grants and fellowships from the Hungarian National Research, Development and Innovation Office (NKFIH NN-127933 and NKFIH K-125977 to AV, NKFIH K-119653 and NVKP_16-2016-1-0039 to AM, NKFIH K-119287 to GT, and NKFIH UK_GYAK-2018-00004 to VL). This research was also funded in part by the Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health (1ZIAHG000183-20 to SB). The research project was part of the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office (TKP2020-IKA-05), and National Institutes of Health Grant R01AR072695 to AV.
Department of Genetics, ELTE Eötvös Loránd University, Budapest, Hungary
Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Division of Biosciences, University College London, London, United Kingdom
Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China
Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, United States
Export Date: 4 May 2021
Correspondence Address: Varga, M.; Department of Genetics, Hungary; email: mvarga@ttk.elte.hu
Correspondence Address: Váradi, A.; Institute of Enzymology, Hungary; email: varadi.andras@ttk.hu
Funding details: National Institutes of Health, NIH, 1ZIAHG000183-20
Funding details: National Human Genome Research Institute, NHGRI
Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K-125977, NKFIH K-119287, NKFIH K-119653, NKFIH UK_GYAK-2018-00004, NN-127933, NVKP_16-2016-1-0039
Funding details: National Research, Development and Innovation Office, R01AR072695, TKP2020-IKA-05
Funding text 1: This work was funded by grants and fellowships from the Hungarian National Research, Development and Innovation Office (NKFIH NN-127933 and NKFIH K-125977 to AV, NKFIH K-119653 and NVKP_16-2016-1-0039 to AM, NKFIH K-119287 to GT, and NKFIH UK_GYAK-2018-00004 to VL). This research was also funded in part by the Intramural Research Program of the National Human Genome Research Institute; National Institutes of Health (1ZIAHG000183-20 to SB). The research project was part of the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office (TKP2020-IKA-05), and National Institutes of Health Grant R01AR072695 to AV. |
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