A Handbook of Mouse Models of Cardiovascular Disease
The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely valuable biomedical tools. Their suitability as an experimental system for cardiovascular research depends on the individual investigator’s ability to manipulate the mice surgically. Many mouse models require microsurgical techniques, which hitherto could not be performed without practical training. This comprehensive handbook enables scientists to develop these models in their own laboratories. A Handbook of Mouse Models of Cardiovascular Disease is the first book to address pathology in mouse models of heart disease, providing the reader with essential information on technical assays in artificially created models. It includes background information on individual cardiovascular diseases, describes detailed methods and materials used for establishing each mouse model, discusses the problems that may appear in the experiments, and provides examples of applications of the model. A Handbook of Mouse Models of Cardiovascular Disease: Describes mouse models of all important cardiovascular diseases, including atherosclerosis, atrial fibrillation and thrombosis Features videos of key experimental procedures on the accompanying CD, allowing researchers to learn the techniques by directly watching the whole operational procedure Describes how to establish each experimental model with detailed protocols and tips on dealing with common operational problems Highlights potential applications of each model in areas such as pathogenesis, gene transfer, therapy and pathophysiology This handbook is an invaluable resource for researchers in cardiovascular disease, pathology, physiology, interested in the mechanism of vascular disorders and therapeutic approaches. It is also relevant to clinicians seeking to understand the pathology of cardiovascular disease and the rationale for interventions, and of interest to the pharmaceutical industry and all those involved in drug discovery/development for cardiovascular disease.
Preface xi List of Contributors xiii 1 Mice – general information 1Hermann Dietrich Historical perspective of house mice as laboratory animals 1 Maintaining and breeding of mice 3 Mouse genetics 5 Blood and bone marrow collection methods 7 Anesthesia and analgesia 7 Euthanasia 14 References 14 2 Naturally occurring variation among mouse strains 19Weibin Shi and Aldons J. Lusis Introduction 19 Mapping genes underlying quantitative traits 20 Dissecting QTLs using congenic strains 22 Testing candidate genes in QTL regions 24 Functional tests of candidate genes 26 From mouse to man 28 References 28 3 Transgenic and gene-targeted mice in the study of hyperlipidemia 33Yadong Huang Introduction 33 Generation of transgenic mouse models 34 Generation of gene-targeted mouse models 36 Application of transgenic and gene-targeted mouse models in hyperlipidemia research 38 Acknowledgments 39 References 40 4 Bone marrow transplantation: the methodology and its application in atherosclerosis research 43Menno P.J. de Winther and Marten H Hofker Introduction 43 Methods 45 Discussion and application 48 Conclusions 50 References 51 5 Hyperlipidemia-induced atherosclerosis 53Alan Daugherty and Debra L. Rateri Introduction 53 Induction of hyperlipidemia in mice 54 Mouse strain 56 Environmental factors 57 Gender 57 Analysis of atherosclerotic lesions 57 Determination of lesion composition 62 Statistical analysis 63 Conclusions 64 Acknowledgments 64 References 64 6 Magnetic resonance imaging evaluation of atherosclerotic plaque 67Martina A. McAteer, Jürgen E. Schneider and Robin P. Choudhury Introduction 67 Imaging atherosclerosis with MRI 68 Mouse MRI 68 Materials and methods 69 Discussion 75 Application 76 Acknowledgments 76 References 76 7 Plaque rupture 79Christopher L. Jackson Introduction 79 Animals 79 Husbandry and welfare 81 Termination 81 Tissue processing 82 Morphological analysis 83 Morphometric analysis 84 Study design considerations 85 Summary 85 Acknowledgment 86 References 86 8 Perivascular cuff-, electronic and chemical injury-induced stenosis 89Nuno M.M. Pires, Margreet R. de Vries, Abbey Schepers, Daniel Eefting, Jan-Willem H.P. Lardenoye and Paul H.A. Quax Introduction 89 Materials and methods 92 Discussion 93 Application 94 References 100 9 Flow-induced vascular remodeling 103Vyacheslav A. Korshunov and Bradford C. Berk Introduction 103 Materials and methods 104 Discussion 107 Applications 108 References 110 Movie legends 111 10 Vein graft atherosclerosis 113Yanhua Hu and Qingbo Xu Introduction 113 Materials and methods 114 Discussion 119 Applications 120 Acknowledgments 122 References 122 11 Angiotensin II-induced aortic aneurysms 125Yi-Xin Wang, Lisa A. Cassis and Alan Daugherty Introduction 125 Methods 126 Discussion 133 Acknowledgments 133 References 134 12 Carotidojugular fistula 137Yves Castier, Alain Tedgui and Stéphanie Lehoux Introduction 137 Creation of the AVF 138 Hemodynamic and structural data 142 References 144 13 Applications to the study of stroke 147Jacques Seylaz and Elisabeth Pinard Introduction 147 Experimental preparation of mice 148 Methods 153 Applications 155 References 157 14 Identifying congenital heart defects in embryos using high-resolution magnetic resonance imaging 159Jürgen E Schneider and Shoumo Bhattacharya Introduction 159 Identifying mouse cardiac malformations 160 Magnetic resonance imaging 160 Embryo MRI technique and analysis 161 Discussion 166 Applications 166 Pros and cons of ex vivo MRI 169 Acknowledgments 169 References 170 15 Allograft arteriopathy: heterotopic heart transplantation and aortic interposition grafts 173Koichi Shimizu and Richard N. Mitchell Introduction 173 Murine models for AA 175 Murine heterotopic cardiac transplantation 177 Murine aortic interposition grafts 183 Translation to clinical investigation 187 References 189 16 Heart preconditioning analysis 193Guang-Wu Wang, David A Liem, Steven Le and Peipei Ping Introduction 193 Methods 194 Methodological considerations 198 References 200 17 Myocardial ischemia–reperfusion 203Bernhard Metzler, Elisabetta Conci and Otmar Pachinger Myocardial ischemia–reperfusion 203 Ischemia–reperfusion models 206 Measurement of infarction size 210 Electrocardiogram and in vivo left ventricular pressure–volume measurements 214 Different mouse types 215 Conclusion 217 References 217 18 Cardiac hypertrophy 221David J. Grieve, Alison C. Cave and Ajay M. Shah Introduction 221 Materials and methods 222 Summary 231 Acknowledgments 231 References 231 19 The retrogradely perfused isolated heart model 235Mihaela M. Mocanu and Derek M. Yellon Introduction 235 Langendorff system 235 Preparation of hearts for perfusion 237 Experimental protocol 241 Measurement of infarct size 242 Infarct size computation 243 General comments 244 Acknowledgments 244 References 244 20 Measurement of pulse wave velocity 245Yi-Xin Wang Introduction 245 Materials and methods 246 Discussion 249 Application 251 References 252 21 Gene transfer to dyslipidemic mice 255Kazuhiro Oka, Andrew H. Baker and Lawrence Chan Introduction 255 Mouse models of dyslipidemia 256 ApoB transgenic mice 263 Vectors for liver-directed gene transfer 263 Route or vector delivery 267 Conclusion 268 Acknowledgments 269 References 269 22 Hypertension 273Daiana Weiss and W. Robert Taylor Introduction 273 Pharmacological models of hypertension 275 Renal models of hypertension 278 Genetic models of hypertension 279 Measurement of blood pressure in mice 282 Summary 282 References 283 23 Ischemia-induced neovascularisation 287Ken-ichiro Sasaki, Christopher Heeschen, Alexandra Aicher and Stefanie Dimmeler Introduction 287 Materials and methods 288 Discussion 296 Application 296 References 297 24 Angiogenesis in biomatrices and artificial materials 299Pieter Koolwijk and Victor W.M. van Hinsburgh Introduction 299 Materials and methods 300 Discussion 305 Application 307 Acknowledgments 308 References 308 25 Venous thrombosis 311Alberto Smith, James Gossage, Matthew Waltham, Bijan Modarai and Julie Humphries Background 311 Models of thrombosis 313 The St Thomas’ model 314 References 319 26 Virus-induced vasculitis 321Philippe Krebs and Burkhard Ludewig Introduction 321 Materials and methods 322 Discussion 329 Application 329 References 330 27 Surgically induced chronic heart failure 333Craig A. Lygate and Stefan Neubauer Introduction 333 Materials and methods 336 Discussion 340 Applications 346 Conclusions 346 References 347 28 Cardiac electrophysiology 349Sander Verheule, Toshiaki Sato and Jeffrey E. Olgin Introduction 349 Anesthesia for adult mice 350 ECG recording and analysis 351 Transesophageal stimulation 352 Open chest epicardial measurements 354 Studies on Langendorff perfused hearts 357 Conclusion 360 References 361 29 Ligation- and wire injury-induced stenosis 363Volkhard Lindner Introduction 363 Materials and methods 364 Discussion 367 Acknowledgments 370 References 370 Index 373
Qingbo Xu. John Parker Professor of Vascular Biology, Department of Cardiac and Vascular Sciences, St George's Hospital Medical School. Professor Xu has an excellent standing in the field of atherosclerosis with an outstanding scientific track record. He is part of a European Network of Excellence on vascular biology, which is a large consortium of experts. He is an expert in mouse models and in microsurgery. His group pioneers the study of heat shock proteins in atherogenesis and has established the first mouse model of vein graft atherosclerosis, which is proven to be powerful in studying the mechanisms of progenitor cells participating in atherosclerosis. Professor Xu’s group also generated the first PKC knockout mice and analysed protein profiles of cardiovascular cells in these mice.
The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely valuable biomedical tools. Their suitability as an experimental system for cardiovascular research depends on the individual investigator’s ability to manipulate the mice surgically. Many mouse models require microsurgical techniques, which hitherto could not be performed without practical training. This comprehensive handbook will enable scientists to develop these models in their own laboratories. It contains detailed advice on the issues that investigators need to consider before starting their experiments. It then provides essential information about experimental procedures, specific instruments and technical knowledge and will prove an indispensable guide to all scientists planning to work with these mouse models. This book includes a brief introduction to each disease, followed by a detailed description of the methods and materials used to establish the relevant mouse model. Each chapter has been written by an expert familiar with that system, who provides helpful discussion of the problems that may be encountered and examples of applications of the model. Importantly, each technique is clearly illustrated on the accompanying CD, so that researchers can observe the operational procedures directly. With coverage of all the major mouse models of cardiovascular disease, this book may be used to obtain a broad overview of commonly used methods and, more importantly, as a comprehensive source of detailed information on the development and study of such models. It will prove essential reading to all those working on experimental animal models of cardiovascular disease, from students to independent investigators.
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