Mouse Models of Cancer: A Laboratory Manual

Subject Area(s): Developmental Biology; Molecular Biology; Mouse Biology; Cancer Biology; Laboratory Techniques

Edited by Cory Abate-Shen, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, Columbia University Medical Center; Katerina Politi, Yale Cancer Center, Yale University School of Medicine; Lewis Chodosh, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania; Kenneth P. Olive, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center

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Preface and Contents
Transgenic Mouse Models—A Seminal Breakthrough in Oncogene Research
Index

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Description
Contents

Description

The laboratory mouse is an important model for addressing questions in cancer biology. In recent years, the questions have become more refined, and mouse models are increasingly being used to develop and test cancer therapeutics. Thus, the need for more sophisticated and clinically relevant mouse models has grown, as has the need for innovative tools to analyze and validate them.

This laboratory manual provides cutting-edge methods for generating and characterizing mouse models that accurately recapitulate many features of human cancer. The contributors describe strategies for producing genetic models, including transgenic germline models, gene knockouts and knockins, and conditional and inducible systems, as well as models derived using transposon-based insertional mutagenesis, RNA interference, viral-mediated gene delivery, and chemical carcinogens. Tissue recombination, organ reconstitution, and transplantation methods to develop chimeric, allograft, and xenograft models are covered. Approaches to characterize tumor development, progression, and metastasis in these models using state-of-the-art imaging, histopathological, surgical, and other techniques are also included.

Other chapters cover the use of mouse models to test and optimize drugs in pre-, co-, and post-clinical trials. An appendix specifically addresses the use of mouse cancer models in translational studies and the integration of mouse and human clinical investigations. This manual is therefore an indispensable laboratory resource for all researchers, from the graduate level upwards, who study cancer and its treatment.

Preface
INTRODUCTION
Of Model Pets and Cancer Models: An Introduction to Mouse Models of Cancer: Andrea Lunardi, Caterina Nardella, John G. Clohessy, and Pier Paolo Pandolfi
PART 1: ORIGINS AND HISTORY OF MOUSE MODELS OF CANCER
CHAPTER 1
INTRODUCTION
Transgenic Mouse Models—A Seminal Breakthrough in Oncogene Research: Harvey W. Smith and William J. Muller
CHAPTER 2
INTRODUCTION
Analyses of Tumor-Suppressor Genes in Germline Mouse Models of Cancer: Jingqiang Wang and Cory Abate-Shen
CHAPTER 3
INTRODUCTION
Conditional Knockout Mouse Models of Cancer: Chu-Xia Deng
CHAPTER 4
INTRODUCTION
Animal Models of Chemical Carcinogenesis: Driving Breakthroughs in Cancer Research for 100 Years: Christopher J. Kemp
PROTOCOLS
1 Induction of Liver Tumors in Mice with N-Ethyl-N-Nitrosourea or N-Nitrosodiethylamine: Kay E. Gurley, Russell D. Moser, and Christopher J. Kemp
2 Induction of Lung Tumors in Mice with Urethane: Kay E. Gurley, Russell D. Moser, and Christopher J. Kemp
3 Induction of Colon Cancer in Mice with 1,2-Dimethylhydrazine: Kay E. Gurley, Russell D. Moser, and Christopher J. Kemp
CHAPTER 5
INTRODUCTION
The Effects of Genetic Background of Mouse Models of Cancer: Friend or Foe?: Karlyne M. Reilly
PROTOCOLS
1 Controlling Genetic Background in Crosses of Mouse Models of Cancer: Karlyne M. Reilly
2 Using the Collaborative Cross to Study the Role of Genetic Diversity in Cancer-Related Phenotypes: Karlyne M. Reilly
PART 2: RECENT APPROACHES TO MODELING CANCER IN MICE
CHAPTER 6
INTRODUCTION
Genetically Engineered Knock-In and Conditional Knock-In Mouse Models of Cancer: Amy Rappaport and Leisa Johnson
CHAPTER 7
INTRODUCTION
Strategies to Achieve Conditional Gene Mutation in Mice: Jessica J. Gierut, Tyler E. Jacks, and Kevin M. Haigis
PROTOCOLS
1 Producing and Concentrating Lenti-Cre for Mouse Infections: Jessica J. Gierut, Tyler E. Jacks, and Kevin M. Haigis
2 In Vivo Delivery of Lenti-Cre or Adeno-Cre into Mice Using Intranasal Instillation: Jessica J. Gierut, Tyler E. Jacks, and Kevin M. Haigis
3 Whole-Mount X-Gal Staining of Mouse Tissues: Jessica J. Gierut, Tyler E. Jacks, and Kevin M. Haigis
CHAPTER 8
INTRODUCTION
Tetracyline-Regulated Mouse Models of Cancer: Elizabeth S. Yeh, Ann Vernon-Grey, Heather Martin, and Lewis A. Chodosh
CHAPTER 9
INTRODUCTION
The Estrogen Receptor Fusion System in Mouse Models: A Reversible Switch: Jonathan Whitfield, Trevor Littlewood, Gerard I. Evan, and Laura Soucek
PROTOCOL
1 Tamoxifen Administration to Mice: Jonathan Whitfield, Trevor Littlewood, and Laura Soucek
CHAPTER 10
INTRODUCTION
Using the RCAS-TVA System to Model Human Cancer in Mice: Leanne G. Ahronian and Brian C. Lewis
PROTOCOLS
1 Generation of High-Titer RCAS Virus from DF1 Chicken Fibroblasts: Leanne G. Ahronian and Brian C. Lewis
2 In Vivo Delivery of RCAS Virus to Mice: Leanne G. Ahronian and Brian C. Lewis
CHAPTER 11
INTRODUCTION
Transposon Insertional Mutagenesis Models of Cancer: Karen M. Mann, Nancy A. Jenkins, Neal G. Copeland, and Michael B. Mann
CHAPTER 12
INTRODUCTION
Accelerating Cancer Modeling with RNAi and Nongermline Genetically Engineered Mouse Models: Geulah Livshits and Scott W. Lowe
CHAPTER 13
INTRODUCTION
Chimeric Tumor and Organ Transplantation Models: Michael Hemann
PROTOCOLS
1 Reconstitution of Mice with Modified Hematopoietic Stem Cells: Michael Hemann
2 Reconstitution of Mice with Modified Liver Stem Cells: Lars Zender and Michael Hemann
3 Syngeneic Transplants with Modified Chimeric Hematopoietic Tumors: Michael Hemann
4 Loss-of-Function Screening in Hematopoietic Malignancies: Michael Hemann
CHAPTER 14
INTRODUCTION
Tissue Recombination Models for the Study of Epithelial Cancer: Yang Zong, Andrew S. Goldstein, and Owen N. Witte
PROTOCOLS
1 Preparation of Urogenital Sinus Mesenchymal Cells for Prostate Tissue Recombination Models: Yang Zong, Andrew S. Goldstein, and Owen N. Witte
2 Dissociated Prostate Regeneration Under the Renal Capsule: Yang Zong, Andrew S. Goldstein, and Owen N. Witte
3 The Cleared Mammary Fat Pad Transplantation Assay for Mammary Epithelial Organogenesis: Devon A. Lawson, Zena Werb, Yang Zong, and Andrew S. Goldstein
CHAPTER 15
INTRODUCTION
Human Cancer Growth and Therapy in Immunodeficient Mouse Models: Leonard D. Shultz, Neal Goodwin, Fumihiko Ishikawa, Vishnu Hosur, Bonnie L. Lyons, and Dale L. Greiner
PROTOCOL
1 Subcapsular Transplantation of Tissue in the Kidney: Leonard D. Shultz, Neal Goodwin, Fumihiko Ishikawa, Vishnu Hosur, Bonnie L. Lyons, and Dale L. Grei
PART 3: ANALYZING MOUSE CANCER PHENOTYPES
CHAPTER 16
INTRODUCTION
Analysis of Mouse Model Pathology: A Primer for Studying the Anatomic Pathology of Genetically Engineered Mice: Robert D. Cardiff, Claramae H. Miller, and Robert J. Munn
PROTOCOLS
1 Limited Mouse Necropsy: Robert D. Cardiff, Claramae H. Miller, and Robert J. Munn
2 Mouse Tissue Fixation: Robert D. Cardiff, Claramae H. Miller, and Robert J. Munn
3 Manual Hematoxylin and Eosin Staining of Mouse Tissue Sections: Robert D. Cardiff, Claramae H. Miller, and Robert J. Munn
4 Manual Immunohistochemistry Staining of Mouse Tissues Using the Avidin-Biotin Complex (ABC) Technique: Robert D. Cardiff, Claramae H. Miller, and Robert J. Munn
CHAPTER 17
INTRODUCTION
Imaging Mouse Cancer Models In Vivo Using Reporter Transgenes: Scott K. Lyons, P. Stephen Patrick, and Kevin M. Brindle
CHAPTER 18
INTRODUCTION
Noninvasive Imaging of Tumor Burden and Molecular Pathways in Mouse Models of Cancer: Yuchuan Wang, Jen-Chieh Tseng, Yanping Sun, Andrew H. Beck, and Andrew L. Kung
PROTOCOLS
1 18F-FDG-PET/CT Imaging of Drug-Induced Metabolic Changes in Genetically Engineered Mouse Lung Cancer Models: Yuchuan Wang and Andrew L. Kung
2 Preclinical Magnetic Resonance Imaging in Mouse Cancer Models: Yanping Sun and Andrew L. Kung
3 Quantitative Bioluminescence Imaging of Mouse Tumor Models: Jen-Chieh Tseng and Andrew L. Kung
CHAPTER 19
INTRODUCTION
Methods to Study Metastasis in Genetically Modified Mice: Farhia Kabeer, Levi J. Beverly, Guillaume Darrasse-Jèze, and Katrina Podsypanina
PROTOCOLS
1 Tissue Dissociation for Metastasis Studies: Farhia Kabeer and Katrina Podsypanina
2 Murine Stem Cell-Based Retrovirus Production for Marking Primary Mouse Mammary Cells for Metastasis Studies: Levi J. Beverly and Katrina Podsypanina
3 Enrichment of Mammary Basal and Luminal Cells for Cell-of-Origin Metastasis Studies: Farhia Kabeer, Katrina Podsypanina, and Guillaume Darrasse-Jèze
4 Isolating Epithelial and Epithelial-to-Mesenchymal Transition Populations from Primary Tumors by Fluorescence-Activated Cell Sorting: Nicole M. Aiello, Andrew D. Rhim, and Ben Z. Stanger
5 Orthotopic Injection of Pancreatic Cancer Cells: Nicole M. Aiello, Andrew D. Rhim, and Ben Z. Stanger
CHAPTER 20
INTRODUCTION
Methods for Analysis of the Immune System in Mouse Cancer Models: Lauren J. Bayne and Robert H. Vonderheide
PROTOCOLS
1 Multicolor Flow Cytometric Analysis of Immune Cell Subsets in Tumor-Bearing Mice: Lauren J. Bayne and Robert H. Vonderheide
2 Immunohistochemical Assessment of Immune Cells in Mouse Tumor Tissue: Lauren J. Bayne and Robert H. Vonderheide
3 A Myeloid-Derived Suppressor Cell-Mediated T-Cell Suppression Assay for Functional Evaluation of Immune Cells in Tumor-Bearing Mice: Lauren J. Bayne and Robert H. Vonderheide
CHAPTER 21
INTRODUCTION
Culturing Mouse Tumor Cells: Andrew D. Rhim, Martin Jechlinger, and Anil K. Rustgi
PROTOCOLS
1 Culturing Primary Mouse Pancreatic Ductal Cells: Maximilian Reichert, Andrew D. Rhim, and Anil K. Rustgi
2 Creation of Primary Cell Lines from Lineage-Labeled Mouse Models of Cancer: Andrew D. Rhim
3 Organotypic Culture of Untransformed and Tumorigenic Primary Mammary Epithelial Cells: Martin Jechlinger
4 Culturing Adult Stem Cells from Mouse Small Intestinal Crypts: Kathryn E. Hamilton, Mary Ann S. Crissey, John P. Lynch, and Anil K. Rustgi
5 Three-Dimensional Organotypic Culture of Stratified Epithelia: Andrew D. Rhim and Anil K. Rustgi
CHAPTER 22
INTRODUCTION
Translational Therapeutics in Genetically Engineered Mouse Models of Cancer: Kenneth P. Olive and Katerina Politi
PROTOCOLS
1 Acquisition of Mouse Tumor Biopsies through Abdominal Laparotomy: Stephen A. Sastra and Kenneth P. Olive
2 Generation of Drug-Resistant Tumors Using Intermittent Dosing of Tyrosine Kinase Inhibitors in Mouse: Valentina Pirazzoli and Katerina Politi
APPENDICES
A. APPLICATIONS FOR GEMMs IN CLINICAL RESEARCH
APPENDIX A1
Effective Utilization and Appropriate Selection of Genetically Engineered Mouse Models for Translational Integration of Mouse and Human Trials: Cory Abate-Shen and Pier Paolo Pandolfi
APPENDIX A2
Infrastructure Needs for Translational Integration of Mouse and Human Trials: John G. Clohessy and Elisa de Stanchina
APPENDIX A3
Structured Reporting in Anatomic Pathology for Coclinical Trials: The caELMIR Model: Robert D. Cardiff, Claramae H. Miller, Robert J. Munn, and Jose J. Galvez
APPENDIX A4
Mouse to Human Blood-Based Cancer Biomarker Discovery Strategies: Samir M. Hanash and Ayumu Taguchi
APPENDIX A5
Evaluation of Cancer Immunity in Mice: Mary L. Disis and Karolina Palucka
APPENDIX A6
Cross-Species Analysis of Mouse and Human Cancer Genomes: Carla Daniela Robles-Espinoza and David J. Adams
B. GENERAL SAFETY AND HAZARDOUS MATERIAL INFORMATION
APPENDIX B
General Safety and Hazardous Material Information
Index