Pathology of Genetically Engineered and Other Mutant Mice

1 Cover

2 Title Page

3 Copyright Page

4 List of Contributors

5 Preface and Acknowledgments

6 1 Introduction to Mouse Pathology The Use of Mice in Medical Research Understanding Diseases Found in Mutant Animals Mouse Pathology – Nomenclature Mouse Genetic Nomenclature Tumor Pathology Immunohistochemistry (IHC), Scoring, Image Analysis, and Other Supportive Research Pathology Techniques Publication of Erroneous Pathology Data: Inadvertent Fraud? Overall Organization of the Book Acknowledgments References

7 2 The Mouse Online: Open Mouse Biology and Pathology Data Resources for Biomedical Research Introduction FAIR Data Access and Databases of Databases General Information on Inbred Laboratory Mice Large Scale Mutagenesis Background Strain Comparison Studies Mouse Pathology Image (Histopathology) Resources Organ/Disease Specific Resources Finding Mouse Models Use of Mouse Pathology Resources on Line; Citations, and Licenses Acknowledgments References

8 3 Mouse Genetic Nomenclature Introduction Why Use Standardized Nomenclature? Inbred Mice Hybrid Mice (F1 and F2) Recombinant Inbred (RI) and Recombinant Congenic Mice Collaborative Cross (CC) Mice Congenic Mice Consomic Mice Conplastic Mice Outbred Mice Diversity Outbred (DO) Mice Nomenclature for Normal and Mutated Genes Spontaneous Mutations in Mice Non‐engineered Induced Mutations Chromosomal Aberration Nomenclature Genetically Engineered Mice Targeted, Endonuclease‐Mediated, Enhancer or Gene Trap, Transposon‐Induced, and Transgenic Mutations Summary Acknowledgments References

9 4 Discovering and Validating Mouse Models of Human Diseases: The Cinderella Effect Introduction Basic Concepts of Defining a Mouse Model for a Human Disease Large‐Scale Mutagenesis Projects to Discover New Mouse Models From Human Polymorphism to Mouse Models New Mouse Genetic Tools Patient Derived Xenograft (PDX) Models Acknowledgments References

10 5 Embryos, Placentas, and Neonates Introduction Four‐Dimensional Anatomy of the Developing Mouse Technical Considerations for Pathologic Evaluation of Developing Mice Pathologic Patterns in Mouse Embryos and Neonates Pathologic Patterns in Mouse Placenta Summary References

11 6 Ciliopathies Introduction Motile Ciliopathies Sensory Ciliopathies Genetic Background Effects References

12 7 Hematopoietic and Lymphoid Tissues Introduction Bone Marrow Lymphoid Tissues Acknowledgments References

13 8 Mouse Hematolymphoid Neoplasms Introduction and Overview of the Classification of Leukemias and Lymphomas in the Mouse Nonlymphoid Hematopoietic Neoplasms in Mice Nonlymphoid Hematopoietic Sarcomas Lymphoid Neoplasms Final Considerations Acknowledgments References

14 9 Immunodeficient and Humanized Mice Introduction Uses of Immunodeficient Mouse Models Common Lesions in Immunodeficient Mice References

15 10 Skin, Hair, and Nails Introduction Normal Anatomy and Embryology of Mouse Skin, Hair, and Nails Practical Guidelines for the Biological Characterization of a New Mutation Categories of Disease of the Skin and Adnexa Skin Cancers Bullous and Acantholytic Skin Diseases: Pemphigus, Pemphigoid, and Epidermolysis Bullosa Structural and Growth Defects in Nails Summary Acknowledgments References

16 11 Mammary Gland Introduction Anatomy, Histology, and Biology of Mouse Mammary Glands Mammary Gland Biology Pathology of the Mammary Gland Neoplastic Progression Mammary Tumor Invasion and Metastases Genetic Engineering of Mouse Mammary Gland Promoters Oncogenes and Tumor Suppressors Oncogene Addiction and Nononcogene Addiction (NOA) Metaplasia Host and Environmental Factors GEM Mammary Tumors Pathology Preparation of Mammary Gland Whole Mounts Preparation of Lung Whole Mounts Case Study: 129S6/ SvEvTac‐Stat 1 tm1RdsMammary Biology and Tumorigenesis (Figures 11.2, 11.7, and 11.10) Summary Internet Resources References

17 12 The Respiratory Tract Introduction The Upper Respiratory Tract The Lung Disease Models References

18 13 The Gastrointestinal Tract Introduction Stomach The Small and Large Intestine References

19 14 Cardiovascular System Mouse Anatomy, Histology, and Physiology Special Necropsy Organ Protocols Genetically Engineered Mice (GEMs) Models of Heart and Vessel Disease Acknowledgments References

20 15 Liver and Pancreas Liver Exocrine Pancreas References

21 16 Neuromuscular System Introduction General Guidelines Histopathology References

22 17 Endocrine System Overview General Phenotypic Considerations for the Endocrine System Pituitary Gland Thyroid Gland Parathyroid Gland Adrenal Gland Pancreatic Islets Pineal Gland References

23 18 Kidney and Urinary Bladder Introduction Mouse Kidney Development, Anatomy, and Histology Pathology of the Mouse Kidney Characterization of Kidney Disease Phenotypes in Mice: Clinical Pathology Glomerular Numbers Preparation of Kidneys for the Histopathology Morphologic Examination Glomerular Diseases Tissue Assessment of Immunologic Disease in Mouse Models Mouse Models of Human Glomerular Diseases Pathology and Scoring of Mouse Renal Glomerular Lesions Systemic Lupus Erythematosus Virus‐Associated Kidney Diseases Renal Tubular Disease Human Genetic Disorders of Tubules Mouse Models of Cystic Kidney Disease Spontaneous Tubular Lesions of Mice Renal Tumors Urinary Bladder: Anatomy and Histology Fixation and Trimming of Urinary Bladder Urinary Bladder Physiology Urolithiasis Urinary Bladder Neoplasia Conclusion References

24 19 Female Reproductive System Embryology and Normal Anatomy of Organs of the Female Reproductive Tract Biological Characterization of a New Mutation of Female Reproductive Tract Spontaneous or Induced Mutant Phenotypes of the Gonads and Receptors Models of Diseases Affecting the Female Reproductive Tract Aging/Spontaneous Strain Specific Lesions Acknowledgments References

25 20 Male Reproductive System Introduction Male Reproductive System Accessory Sex Glands Preputial Glands Bulbourethral Glands (Cowper's Glands) Ampullary Glands Periurethral Glands (Glands of Littré) Seminal Vesicles Prostate Adenocarcinoma Sarcomatoid Carcinoma Neuroendocrine Carcinoma Specific Prostatic Tumor Models Testes and Epididymis Aging and Spontaneous Strain‐Specific Lesions Miscellaneous Changes Genetically Engineered Mouse Models of Male Infertility Tubule and Sertoli Cell Vacuolation Neoplasms of the Testis Sex Cord‐Stromal Tumors References

26 21 Nervous System Anatomy, Histology, and Physiology Genetically Engineered Mice (GEM) Disease Models: Degenerative References

27 22 Eye and Ear Anatomy, Histology, and Physiology of the Eye Tissue Processing and Sectioning – Paraffin Embedded Samples References

28 23 Bones and Teeth Introduction Bone Phenotyping Mouse Bone Diseases of Bone Teeth Acknowledgments References

29 Index

30 End User License Agreement

1 Chapter 2 Table 2.1 Websites with information useful for phenotyping mutant laborator... Table 2.2 SNP comparison between inbred strains for the Abcc6 gene. A search of t... Table 2.3 Polymorphisms in Adh7. Two SNP in the Adh7 gene (formerly called Adh4 ) ... Table 2.4 Sources of mouse models for human diseases.

2 Chapter 3 Table 3.1 Types of mouse strains. Table 3.2 Standardized nomenclature. Table 3.3 Inbred strains of mice. Table 3.4 Inbred strain nomenclature. Table 3.5 Examples of inbred strain abbreviations. Table 3.6 F1 and F2 hybrid mice. Table 3.7 Breeding data used to identify the gene responsible for the hair ... Table 3.8 Recombinant inbred and recombinant congenic strain designation. Table 3.9 Congenic strains. Table 3.10 Outbred mouse stocks. Table 3.11 Evolution of the nomenclature for nude. Table 3.12 Nomenclature for spontaneous mouse mutations. Table 3.13 Nomenclature for transgenic mice.