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Zhenguang Zhang University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Agnes E Coutinho University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Tak Yung Man University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Tiina M J Kipari Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK

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Patrick W F Hadoke University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Donald M Salter Centre for Genomic and Experimental Medicine, MRC Institute of Genetic and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, UK

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Jonathan R Seckl University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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Karen E Chapman University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

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.1161/ATVBAHA.111.241364 22207732 Clausen BE Burkhardt C Reith W Renkawitz R Forster I 1999 Conditional gene targeting in macrophages and granulocytes using LysMcre mice . Transgenic Research 8 265 – 277 . ( doi:10.1023/A

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Bernard Freudenthal Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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John Logan Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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Sanger Institute Mouse Pipelines Mouse Pipelines, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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Peter I Croucher Garvan Institute of Medical Research, Sydney, New South Wales, Australia

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Graham R Williams Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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J H Duncan Bassett Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK

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protein-coding genes in C57BL/6 mouse ES cells by 2021 ( Collins et al . 2007 ). The IKMC-targeted mutagenesis techniques involve use of bacterial artificial chromosome (BAC)-based ‘Knockout-First’ conditional ready gene targeting vectors that use

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T V Novoselova Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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R Larder University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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D Rimmington University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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C Lelliott Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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E H Wynn Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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R J Gorrigan Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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P H Tate Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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L Guasti Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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The Sanger Mouse Genetics Project Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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S O’Rahilly University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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A J L Clark Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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D W Logan Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

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A P Coll University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK

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L F Chan Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London, UK

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gene targeting was confirmed by long-range PCR and quantitative PCR. Targeted ES cells were microinjected into blastocysts and used to generate chimeras. Germ-line transmission was confirmed by genotyping PCR analyses ( http

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Noelia Martínez-Sánchez Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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José M Moreno-Navarrete CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain

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Cristina Contreras Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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Eva Rial-Pensado Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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Johan Fernø Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
Department of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway

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Rubén Nogueiras Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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Carlos Diéguez Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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José-Manuel Fernández-Real CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain

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Miguel López Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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M 2015 Surgery-induced weight loss is associated with the down­regulation of genes targeted by microRNAs in adipose tissue . Journal of Clinical Endocrinology and Metabolism 100 E1467 – E1476 . ( doi:10.1210/jc.2015-2357 ) Pearce EN

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S Khan Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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D E W Livingstone Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Centre for Discovery Brain Science, University of Edinburgh, Hugh Robson Building, Edinburgh, UK

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A Zielinska College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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C L Doig Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham, UK

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D F Cobice Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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C L Esteves Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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J T Y Man Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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N Z M Homer Mass Spectrometry Core Laboratory, Edinburgh Clinical Research Facility, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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J R Seckl Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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C L MacKay SIRCAMS, School of Chemistry, University of Edinburgh, Joseph Black Building, King's Buildings, Edinburgh, UK

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S P Webster Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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G G Lavery Department of Biosciences, School of Science & Technology, Nottingham Trent University, Nottingham, UK

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K E Chapman Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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B R Walker Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Clinical & Translational Research Institute, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK

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R Andrew Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Mass Spectrometry Core Laboratory, Edinburgh Clinical Research Facility, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

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Cederquist C Rosen ED , 2013 Lessons on conditional gene targeting in mouse adipose tissue . Diabetes 62 864 – 874 . ( https://doi.org/10.2337/db12-1089 ) Liu J Wang L Zhang A Di W Zhang X Wu L Yu J Zha J Lv S Cheng P , 2011

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Emma Castrique Henry Wellcome Labs for Integrative Neuroscience and Endocrinology, Division of Molecular Neuroendocrinology, Department of Cellular and Molecular Medicine, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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Marta Fernandez-Fuente Henry Wellcome Labs for Integrative Neuroscience and Endocrinology, Division of Molecular Neuroendocrinology, Department of Cellular and Molecular Medicine, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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Paul Le Tissier Henry Wellcome Labs for Integrative Neuroscience and Endocrinology, Division of Molecular Neuroendocrinology, Department of Cellular and Molecular Medicine, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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Andy Herman Henry Wellcome Labs for Integrative Neuroscience and Endocrinology, Division of Molecular Neuroendocrinology, Department of Cellular and Molecular Medicine, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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Andy Levy Henry Wellcome Labs for Integrative Neuroscience and Endocrinology, Division of Molecular Neuroendocrinology, Department of Cellular and Molecular Medicine, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK

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: rapid reversion of acidophilic cell types to pregestational proportions after weaning . Endocrinology 129 1215 – 1220 . Schmidt-Suppiran M Rajewsky K 2007 Vagaries of conditional gene targeting . Nature Immunology 8 665 – 668 . Srinivas

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Colin P Sibley Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK

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Swanson A Kloczko E Boyd M Barker H Avdic-Belltheus A Martin J Zachary I Peebles D 2016 Gene targeting to the uteroplacental circulation of pregnant guinea pigs . Reproductive Sciences 23 1087 – 1095 . ( doi:10

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Pauline Campos College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK

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Jamie J Walker College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK
EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter, UK
Bristol Medical School, Translational Health Sciences, University of Bristol, Bristol, UK

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Patrice Mollard IGF, University of Montpellier, CNRS, INSERM, Montpellier, France

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) Vasileva A Jessberger R 2005 Precise hit: adeno-associated virus in gene targeting . Nature Reviews: Microbiology 3 837 – 847 . ( https://doi.org/10.1038/nrmicro1266 ) Viskaitis P Irvine EE Smith MA Choudhury AI Alvarez-Curto E

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David R Grattan Centre for Neuroendocrinology and Department of Anatomy, Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, PO Box 913, Dunedin 9054, New Zealand
Centre for Neuroendocrinology and Department of Anatomy, Maurice Wilkins Centre for Molecular Biodiscovery, University of Otago, PO Box 913, Dunedin 9054, New Zealand

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function, including gene-targeting approaches that allow conditional regulation of prolactin responsive cells, will provide the impetus for a new wave of research to enhance our understanding of this fascinating system. Sixty years on from Geoffrey Harris

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