16 results on '"Peter, van Hasselt"'
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2. Evolutionary conservation of the fidelity of transcription
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Claire Chung, Bert M. Verheijen, Zoe Navapanich, Eric G. McGann, Sarah Shemtov, Guan-Ju Lai, Payal Arora, Atif Towheed, Suraiya Haroon, Agnes Holczbauer, Sharon Chang, Zarko Manojlovic, Stephen Simpson, Kelley W. Thomas, Craig Kaplan, Peter van Hasselt, Marc Timmers, Dorothy Erie, Lin Chen, Jean-Franćois Gout, and Marc Vermulst
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Science - Abstract
The molecular mechanisms that ensure faithful transcription of genetic information are still unclear. Chung et al. identify various genes, alleles and processes that affect the fidelity of transcription multiple organisms, suggesting evolutionary conservation of fidelity factors, and compare the error rate of transcription among these species.
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- 2023
- Full Text
- View/download PDF
3. ASSiST - A Superconducting Fault Current Limiter in a Public Electric Power Grid
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Thomas Janetschek, Peter Kummeth, Anne Bauer, Peter van Hasselt, Tabea Arndt, Hans Peter Kraemer, Manfred Wohlfart, Michael Frank, and Christian Schacherer
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business.industry ,Computer science ,Electrical engineering ,Superconducting fault current limiters ,Energy Engineering and Power Technology ,Electric power grid ,Electrical and Electronic Engineering ,business - Published
- 2022
4. An in situ cut-and-paste genome editing platform mediated by CRISPR/Cas9 or Cas12a
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Ping Jiang, Kevin M. Kemper, Kai-Ti Chang, Cheng Qian, Yulong Li, Liying Guan, Peter van Hasselt, Salvatore J. Caradonna, and Randy Strich
- Abstract
Recombinant DNA technology mediated by restriction enzymes and ligases allows in vitro manipulation of a DNA segment isolated from the genome. Short overhangs generated by restriction enzymes facilitate efficient pasting together a DNA sequence and a vector. We adopted this recombinant DNA strategy to develop an in vivo recombinant-genome genome editing approach. Using the programmable endonuclease Cas9 or Cas12a as a restriction enzyme, we devised an in situcut-and-paste (iCAP) genome editing method that was tested in both mouse germline and human cell line platforms. Mouse gene loci Slc35f2 and Slc35f6 were each edited with in-frame insertion of a large APEX2-Cre cassette and concurrent FRT3 insertion at a second location providing proof of principle for the iCAP method. Further, a de nova single nucleotide mutation associated with MED13L syndrome was efficiently corrected in patient cells. Altogether, the iCAP method provides a single genome editing platform with flexibility and multiutility enabling versatile and precise sequence alterations, such as insertion, substitution, and deletion, at single or multiple locations within a genomic segment in mammalian genomes.
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- 2022
5. Evolutionary conservation of the fidelity of transcription
- Author
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Claire Chung, Eric McGann, Lambertus Verheijen, Zoe Navapanich, Sarah Shemtov, Guan-Ju Lai, Atif Towheed, Suraiya Haroon, Agnes Holczbauer, Sharon Chang, Zarko Manojlovic, Stephen Simpson, W. Kelley Thomas, Craig Kaplan, Peter van Hasselt, H.Th.Marc Timmers, Dorothy A. Erie, Lin Chen, Jean-Francois Gout, and Marc Vermulst
- Abstract
Accurate transcription is required for the faithful expression of genetic information. Surprisingly though, little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address this issue, we measured the error rate of transcription in five organisms of increasing complexity and identified various genes, alleles and processes that control transcriptional fidelity in multicellular organisms. In doing so, they highlight the evolutionary conservation of fidelity factors and open up new opportunities to probe the impact of transcription errors on intact organisms and human physiology. Finally, our experiments provide the first reasonable estimate of the error rate of transcription in human cells, identify the first disease associated with error-prone RNA polymerases and suggest that transcription errors may have contributed to the evolution of our genetic code.
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- 2022
6. Atidarsagene autotemcel, a European post-regulatory approval model for delivery of autologous hematopoietic stem cell gene therapy products via a network of qualified treatment centers (QTCs)
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Simon Jones, Robert Wynn, Francesca Fumagalli, Valeria Calbi, Alessandro Aiuti, Samuel Groeschel, Caroline Lindemans, Caroline Sevin, Jean-Hugues Dalle, Peter van Hasselt, and Katie Snell
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Genetics ,Molecular Biology ,Biochemistry - Published
- 2023
7. Atidarsagene Autotemcel, a European Post-Regulatory Approval Model for Delivery of Autologous Hematopoietic Stem Cell Gene Therapy Products Via a Network of Qualified Treatment Centers (QTCs)
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Robert F. Wynn, Simon Jones, Francesca Fumagalli, Valeria Calbi, Alessandro Aiuti, Samuel Gröschel, Peter Lang, Peter van Hasselt, Caroline A. Lindemans, Caroline Sevin, Jean-Hugues Dalle, and Katie Snell
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
8. Bilateral posterior lamellar corneal transplant surgery in an infant of 17 weeks old: surgical challenges and the added value of intraoperative optical coherence tomography
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Marc Muijzer, Hester Y. Kroes, Peter Van Hasselt, and Robert Wisse
- Subjects
genetic structures ,sense organs ,eye diseases - Abstract
To describe the surgical challenges, management, and value of intra-operative optical coherence tomography in a case of a bilateral Descemet Stripping Automated Endothelial Keratoplasty corneal transplantation at 17 weeks of age for the treatment of severe posterior polymorphous corneal dystrophy resulting from a de novo mutation of the OVOL2-gene.
- Published
- 2021
9. Fetal bovine serum impacts the observed N‐glycosylation defects in TMEM165 KO HEK cells
- Author
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Climer, Leslie, Morelle, Willy, De Bettignies, Geoffroy, Krzewinski Recchi, Marie-Ange, Lupashin, Vladimir, Medina-Cano, Daniel, Ucuncu, Ekin, Nguyen, Lam Son, Nicouleau, Michael, Lipecka, Joanna, Bizot, Jean-Charles, Thiel, Christian, Lefort, Nathalie, Faivre-Sarrailh, Catherine, Colleaux, Laurence, Guerrera, Ida Chiara, Cantagrel, Vincent, Lebredonchel, Elodie, Garat, Anne, Legrand, Dominique, Decool, Valérie, Klein, André, Ouzzine, Mohamed, Gasnier, Bruno, Potelle, Sven, Groux‐Degroote, Sophie, Cogez, Virginie, Noel, Maxence, Portier, Lucie, Solórzano, Carlos, Dall'Olio, Fabio, Steenackers, Agata, Mortuaire, Marlène, Gonzalez‐Pisfil, Mariano, Henry, Mélanie, Heliot, Laurent, Harduin-Lepers, Anne, Berthe, Audrey, Zaffino, Marie, Muller, claire, Houdou, Marine, Schulz, Céline, Bost, Frédéric, De Fay, Elia, Mazerbourg, Sabine, Flament, Stéphane, Mouajjah, Dounia, Ashikov, Angel, Abu Bakar, Nurulamin, Wen, Xiao-Yan, Niemeijer, Marco, Rodrigues Pinto Osorio, Glentino, Brand-Arzamendi, Koroboshka, Hasadsri, Linda, Hansikova, Hana, Raymond, Kimiyo, Ondruskova, Nina, Simon, Marleen, Pfundt, Rolph, Timal, Sharita, Beumers, Roel, Smeets, Roel, Kersten, Marjan, Huijben, Karin, Linders, Peter, van den Bogaart, Geert, van Hijum, Sacha, Rodenburg, Richard, van den Heuvel, Lambertus, Van Spronsen, Francjan, Honzik, Tomas, van Scherpenzeel, Monique, Lefeber, Dirk, Mirjam, Wamelink, Han, Brunner, Helen, Mundy, Helen, Michelakakis, Peter, van Hasselt, Jiddeke, van de Kamp, Diego, Martinelli, Lars, Morkrid, Katja, Brocke Holmefjord, Jozef, Hertecant, Majid, Alfadhel, Kevin, Carpenter, Johann, te Water Naude, Delos, Maxime, Hellec, Charles, Fifre, Alexandre, Carpentier, Mathieu, Papy-Garcia, Dulce, Allain, Fabrice, Denys, Agnés, Gilormini, Pierre André, Lion, Cédric, Vicogne, Dorothée, Guerardel, Yann, Biot, Christophe, Witters, Peter, Breckpot, Jeroen, Preston, Graem, Morava, Eva, Rujano, Maria, Cannata Serio, Magda, Panasyuk, Ganna, Reunert, Janine, Hauser, Virginie, Park, Julien, Freisinger, Peter, Guida, Maria Clara, Maier, Esther, Wada, Yoshinao, Jäger, Stefanie, Krogan, Nevan, Kretz, Oliver, Nobre, Susana, Garcia, Paula, Quelhas, Dulce, Bird, Thomas, Raskind, Wendy, Schwake, Michael, Duvet, Sandrine, Marquardt, Thorsten, Simons, Matias, Blommaert, Eline, Péanne, Romain, Cherepanova, Natalia, Rymen, Daisy, Staels, Frederik, Jaeken, Jaak, Race, Valérie, Keldermans, Liesbeth, Souche, Erika, Corveleyn, Anniek, Sparkes, Rebecca, Bhattacharya, Kaustuv, Devalck, Christine, Schrijvers, Rik, Foulquier, Francois, Gilmore, Reid, Matthijs, Gert, Université Lille Nord de France (COMUE), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Variabilité génétique des défenses de l'organisme face à son environnement chimique, PRES Université Lille Nord de France-Université de Lille, Droit et Santé, ANR-15-CE14-0001,SOLV_CDG,Décryptage des patients CDG (Congenital Disorders of Glyvosylation) déficients en TMEM165 - de la compréhension des mécanismes moléculaires à une thérapie(2015), ANR-15-RAR3-0004,EURO-CDG-2,A European research network directed towards improving diagnosis and treatment of inborn glycosylation disorders.(2015), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Baylor University, University of Arkansas for Medical Sciences [UAMS], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Key-Obs, JRC Institute for Energy and Transport (IET), European Commission - Joint Research Centre [Petten], Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Impact de l'environnement chimique sur la santé humaine (IMPECS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Biologie cellulaire et moléculaire de la sécrétion (BCMS), Centre National de la Recherche Scientifique (CNRS), Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, Department of Experimental, Diagnostic and Specialty Medicine (DIMES) (DIMES), Università di Bologna [Bologna] (UNIBO), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Biophotonique Cellulaire Fonctionelle, Institut de Recherche Interdisciplinaire, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine & Physiology , University of Toronto, First Faculty of Medicine, Charles University [Prague], University Medical Center [Utrecht], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Paediatrics, Beatrix Children's Hospital/University Medical Center Groningen, Université Toulouse 1 Capitole (UT1), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire et Formulation (EA 4478), Université de Lille, Sciences et Technologies, Unité de Catalyse et de Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, University Children's Hospital, Centre de recherche Croissance et signalisation (UMR_S 845), Reutlingen University, Department of General Pediatrics, Münster University Children Hospital, Molecular Diagnostics, Center for Human Genetics, Gasthuisberg, Katholieke Universiteit Leuven and Flanders Interuniversity Institute for Biotechnology 4, Leuven, Belgium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Center for Human Genetics, and Laboratory of clinical immunology
- Subjects
Glycosylation ,Protein family ,[SDV]Life Sciences [q-bio] ,Golgi Apparatus ,FBS ,manganese level ,N‐glycosylation defects ,TMEM165 ,Article ,Antiporters ,Glycomics ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,Congenital Disorders of Glycosylation ,0302 clinical medicine ,N-linked glycosylation ,Genetics ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Cation Transport Proteins ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Manganese ,0303 health sciences ,Ion Transport ,HEK 293 cells ,Serum Albumin, Bovine ,Golgi apparatus ,Embryonic stem cell ,Cell biology ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,carbohydrates (lipids) ,HEK293 Cells ,chemistry ,symbols ,Calcium ,030217 neurology & neurosurgery ,Fetal bovine serum - Abstract
TMEM165 is involved in a rare genetic human disease named TMEM165‐CDG (congenital disorders of glycosylation). It is Golgi localized, highly conserved through evolution and belongs to the uncharacterized protein family 0016 (UPF0016). The use of isogenic TMEM165 KO HEK cells was crucial in deciphering the function of TMEM165 in Golgi manganese homeostasis. Manganese is a major cofactor of many glycosylation enzymes. Severe Golgi glycosylation defects are observed in TMEM165 Knock Out Human Embryonic Kidney (KO HEK) cells and are rescued by exogenous manganese supplementation. Intriguingly, we demonstrate in this study that the observed Golgi glycosylation defect mainly depends on fetal bovine serum, particularly its manganese level. Our results also demonstrate that iron and/or galactose can modulate the observed glycosylation defects in TMEM165 KO HEK cells. While isogenic cultured cells are widely used to study the impact of gene defects on proteins' glycosylation patterns, these results emphasize the importance of the use of validated fetal bovine serum in glycomics studies. 43;2
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- 2019
10. Verbesserte supraleitende Spulen mit in situ Aushärteverfahren
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Dr. Jörn Grundmann, DE Erlangen, Dr. Michael Frank, DE Erlangen, Dr. Peter Van Hasselt, DE Erlangen, Dr. Thomas Gleixner, DE Erlangen, Dr. Peter Gröppel, DE Erlangen, and Dr. Stefan Moldenhauer
- Subjects
Spulen ,Aushärteverfahren ,supraleitende - Published
- 2019
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11. Concept design of a high power superconducting generator for future hybrid-electric aircraft
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Markus Wilke, Dirk Möller, Martin Thummet, Jörn Grundmann, Marc Lessmann, Matthias Böhm, Johannes Richter, Christian Weidermann, Peter Gröppel, Lars Kühn, Stefan Moldenhauer, Markus Klöpzig, Mercedes Herranz-Garcia, Andreas Schröter, Mykhaylo Filipenko, Arestid Spangolo, Peter van Hasselt, Michael Frank, Thomas Gleixner, and Kerstin Häse
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Materials science ,business.industry ,Superconducting electric machine ,Metals and Alloys ,Electrical engineering ,High voltage ,High power density ,Condensed Matter Physics ,Power (physics) ,law.invention ,law ,Materials Chemistry ,Ceramics and Composites ,Electric aircraft ,Electrical and Electronic Engineering ,business ,Liquid hydrogen - Abstract
The reduction of emission is a key goals for the aviation industry. One enabling technology to achieve this goal, could be the transition from conventional gas turbines to hybrid-electric drive trains. However, the requirements concerning weight and efficiency that come from applications like short range aircraft are significantly higher than what state-of-the-art technology can offer. A key technology that potentially allows to achieve the necessary power and volume densities for rotating electric machines is superconductivity. In this paper we present the concept of a high power density generator that matches the speed of typical airborne turbines in its power class. The design is based on studies that cover topology selection and further electromagnetic, HTS, thermal, structural and cryogenics aspects. All domains were analyzed by means of analytical sizing and 2D/3D FEA modeling. With the help of our digital twin that is a synthesis of these models, we can demonstrate for the first time that under realistic assumptions on material properties gravimetric power densities beyond 20 kW kg−1 can be achieved.
- Published
- 2020
12. Design and Development of a Test Rig for HTS Generator Components
- Author
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Wolfgang Nick, Michael Frank, Anne Kuhnert, Peter Kummeth, Marijn Pieter Oomen, Peter van Hasselt, and Tabea Arndt
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Computer science ,Superconducting electric machine ,Rotor (electric) ,Rotational speed ,Condensed Matter Physics ,Automotive engineering ,Electronic, Optical and Magnetic Materials ,Power (physics) ,law.invention ,Generator (circuit theory) ,law ,Electromagnetic coil ,Water cooling ,Electrical and Electronic Engineering ,Energy source - Abstract
High temperature superconducting (HTS) rotating machines show several significant advantages compared to machines built in conventional technique. Former experiments on rotating electric synchronous machines like motors and generators in the power range up to several MW confirmed the well-known benefits of HTS machines like smaller size, less weight and last but not least, a significantly increased efficiency. Especially the increased efficiency of large HTS-Generators up to several hundreds of MW-as operated by utilities-promises an efficient use of fuel and energy sources. This will allow reduced carbon dioxide emissions and becomes more and more important. The development of HTS rotor technology for generators in the range of hundreds of MW bears new challenges. HTS generator windings capable to withstand large centrifugal forces and carrying large currents are required. Also a special cooling system for the rotating winding and further components with novel design will be necessary and have to be developed. In a future HTS generator based on such components, these will have to operate very reliably, so a facility is needed to be able to perform tests. Therefore it is essential to design and build a specific test rig for investigation and test of the required new components. The present paper deals with design and development of such a test rig that allows component tests under realistic conditions, using radii in the range of 0.45 m as in a generator application at rotational speed of up to 3000 rpm, and at low operating temperatures of about 30 K. Additionally a 3 kA high current power supply for HTS test objects like coils or contacts is projected. Aspects of rotor dynamics and fatigue strength analysis had to be considered.
- Published
- 2015
13. Abschirmung supraleitender Wicklungen gegen AC-Verluste
- Author
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Dr. Michael Frank, DE-Erlangen, Dr. Peter Van Hasselt, DE-Erlangen, and Dr. Peter Kummeth, DE-Erlangen
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- 2016
- Full Text
- View/download PDF
14. Transparantie
- Author
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Luc van Berkestijn and Peter van Hasselt
- Subjects
Family Practice - Published
- 2011
15. Reply
- Author
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Hannelie M. Engbers, Ruud Berger, Peter van Hasselt, Tom de Koning, Monique G. M. de Sain-van der Velden, Hester Kroes, and Gepke Visser
- Subjects
Neurology ,Neurology (clinical) - Published
- 2009
16. Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation.
- Author
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Ashikov A, Abu Bakar N, Wen XY, Niemeijer M, Rodrigues Pinto Osorio G, Brand-Arzamendi K, Hasadsri L, Hansikova H, Raymond K, Vicogne D, Ondruskova N, Simon MEH, Pfundt R, Timal S, Beumers R, Biot C, Smeets R, Kersten M, Huijben K, Linders PTA, van den Bogaart G, van Hijum SAFT, Rodenburg R, van den Heuvel LP, van Spronsen F, Honzik T, Foulquier F, van Scherpenzeel M, Lefeber DJ, Mirjam W, Han B, Helen M, Helen M, Peter VH, Jiddeke VK, Diego M, Lars M, Katja BH, Jozef H, Majid A, Kevin C, and Johann TWN
- Subjects
- Adult, Animals, Bone Diseases, Developmental metabolism, Bone Diseases, Developmental pathology, Cells, Cultured, Cohort Studies, Exome, Female, Fibroblasts metabolism, Fibroblasts pathology, Glycosylation, Golgi Apparatus metabolism, Golgi Apparatus pathology, Humans, Infant, Male, Organic Anion Transporters, Sodium-Dependent metabolism, Pedigree, Phenotype, Protein Transport, Symporters metabolism, Young Adult, Zebrafish genetics, Zebrafish growth & development, Zebrafish metabolism, Bone Diseases, Developmental etiology, Calcification, Physiologic, Congenital Disorders of Glycosylation complications, Genomics, Glycomics, Mutation, Organic Anion Transporters, Sodium-Dependent genetics, Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase deficiency, Symporters genetics
- Abstract
Genomics methodologies have significantly improved elucidation of Mendelian disorders. The combination with high-throughput functional-omics technologies potentiates the identification and confirmation of causative genetic variants, especially in singleton families of recessive inheritance. In a cohort of 99 individuals with abnormal Golgi glycosylation, 47 of which being unsolved, glycomics profiling was performed of total plasma glycoproteins. Combination with whole-exome sequencing in 31 cases revealed a known genetic defect in 15 individuals. To identify additional genetic factors, hierarchical clustering of the plasma glycomics data was done, which indicated a subgroup of four patients that shared a unique glycomics signature of hybrid type N-glycans. In two siblings, compound heterozygous mutations were found in SLC10A7, a gene of unknown function in human. These included a missense mutation that disrupted transmembrane domain 4 and a mutation in a splice acceptor site resulting in skipping of exon 9. The two other individuals showed a complete loss of SLC10A7 mRNA. The patients' phenotype consisted of amelogenesis imperfecta, skeletal dysplasia, and decreased bone mineral density compatible with osteoporosis. The patients' phenotype was mirrored in SLC10A7 deficient zebrafish. Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization. Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane. In contrast to yeast, human SLC10A7 localized to the Golgi. Our combined data indicate an important role for SLC10A7 in bone mineralization and transport of glycoproteins to the extracellular matrix.
- Published
- 2018
- Full Text
- View/download PDF
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