Pathology of genetically engineered and other mutant mice

Description

Cover Title Page Copyright Page Contents List of Contributors Preface and Acknowledgments Chapter 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 Chapter 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 Mouse Genome Informatics (http://www.informatics.jax.org) MouseMine (http://www.mousemine.org/mousemine/begin.do) Monarch (https://monarchinitiative.org) Alliance of Genome Resources (https://www.alliancegenome.org) Mouse Models of Human Cancer Database (MMHC, Formerly Mouse Tumor Biology Database) (http://tumor.informatics.jax.org/mtbwi/index.do) Mouse Genome Informatics SNP Database (http://www.informatics.jax.org/snp) Sanger Mouse SNP Database (https://www.sanger.ac.uk/sanger/Mouse_SnpViewer/rel-1505) Large Scale Mutagenesis International Mouse Phenotyping Consortium (IMPC; https://www.mousephenotype.org) MUTAGENETIX (https://mutagenetix.utsouthwestern.edu) Background Strain Comparison Studies Mouse Phenome Database (https://phenome.jax.org) Mouse Pathology Image (Histopathology) Resources Pathbase, the European Mouse Pathology Database (http://www.pathbase.net) National Toxicology Program Neoplastic Lesion Atlas (https://ntp.niehs.nih.gov/nnl/index.htm) Noah’s Arkive, Charles Louis Davis, and Samuel Wesley Thompson Foundation for the Advancement of Veterinary and Comparative Pathology (http://noahsarkive.cldavis.org/cgi-bin/show_image_info_page.cgi) Organ/Disease Specific Resources Bone Diseases: Skeletal Phenotyping of IMPC/KOMP Mice (http://www.bonebase.org) Skin Diseases: Skinbase (http://eulep.pdn.cam.ac.uk/~skinbase/index.php) GenitoUrinary Development Molecular Anatomy Project (GUDMAP) (https://www.gudmap.org) Mouse Brain Atlas (https://developingmouse.brain-map.org, https://mouse.brain-map.org) Atlas of Mouse Cardiovascular Development (https://www.devbio.pitt.edu/research/atlas-mouse-cardiovascular-development) Mouse/Human Disease Phenotype Databases Online Mendelian Inheritance in Man (OMIM) (https://www.ncbi.nlm.nih.gov/omim) Emouseatlas (https://www.emouseatlas.org/emap/home.html) Finding Mouse Models Use of Mouse Pathology Resources on Line; Citations, and Licenses Acknowledgments References Chapter 3 Mouse Genetic Nomenclature: The Underpinning of Mouse Genetics 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 Chapter 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 Chapter 5 Embryos, Placentas, and Neonates Introduction Four-Dimensional Anatomy of the Developing Mouse Developmental Events in Embryos and Neonates Developmental Events in Placentation Technical Considerations for Pathologic Evaluation of Developing Mice Noninvasive Imaging of Developing Mice Anatomic Pathology Evaluation ofDeveloping Mice Clinical Pathology Evaluation of Developing Mice Pathologic Patterns in Mouse Embryos and Neonates Pathologic Patterns in Mouse Placenta Summary References Chapter 6 Ciliopathies Introduction Motile Ciliopathies Rhinosinusitis and Otitis Media Hydrocephalus Laterality Defects Infertility Sensory Ciliopathies Cystic Kidney Diseases Retinal Degeneration Heart Defects Skeletal Defects Brain Malformations Deafness Anosmia Obesity Genetic Background Effects References Chapter 7 Hematopoietic and Lymphoid Tissues Introduction Bone Marrow Lymphoid Tissues Primary Lymphoid Organs Secondary Lymphoid Organs Tertiary Lymphoid Organs Acknowledgments References Chapter 8 Mouse Hematolymphoid Neoplasms Introduction and Overview of the Classification of Leukemias and Lymphomas in the Mouse Nonlymphoid Hematopoietic Neoplasms in Mice Myeloid Leukemia (Granulocytic Leukemia, Myelogenous Leukemia, and Myelocytic Leukemia) Myelomonocytic Leukemia Monocytic Leukemia Erythroid Leukemia Megakaryocytic Leukemia Mast Cell and Basophil Leukemia Myeloid Proliferations (Nonreactive) Bone Marrow, Spleen, and Other Tissues Myeloid Dysplasia Nonlymphoid Hematopoietic Sarcomas Myeloid Sarcoma Histiocytic Sarcoma Dendritic Cell Tumors/Histiocytosis Mast Cell Neoplasms Lymphoid Neoplasms Overview of Lymphoid Neoplasm Classification B-Cell Neoplasms T-Cell Neoplasia Mature T-Cell Neoplasms Final Considerations Acknowledgments References Chapter 9 Immunodeficient and Humanized Mice Introduction Nude Mice Prkdcscid, Rag1 and Rag2-Deficient,and Lystbg Mice NOD-Prkdcscid Mice IL-2RG-Deficient Mice Uses of Immunodeficient Mouse Models Xenotransplants of Solid and Hematopoietic Human Patient-Derived Tumors or Neoplastic Cell Lines Immunologic Reactions AgainstTransplanted Tumors Humanized Mice Common Lesions in Immunodeficient Mice Experimentally Induced Lesions Naturally Occurring Lesions – Infectious and Parasitic Naturally Occurring Lesions – Noninfectiousor Parasitic References Chapter 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 Hair Color (Pigmentation) Mutations Sebaceous and Eccrine Gland Defects and Scarring Alopecias Hair Follicle Cycling and Structural Defects of Hair Shafts Proliferative Skin Diseases Autoimmune Skin Diseases Skin Cancers Cancer-like Epidermal Response to Injury (Pseudoepitheliomatous/Pseudocarcinomatous Hyperplasia) Spontaneous Nonmelanoma Skin Cancers in Mice Two-stage Chemical Carcinogenesis UV Light-Induced Carcinogenesis Papillomaviruses Mouse Models of Melanoma Bullous and Acantholytic Skin Diseases: Pemphigus, Pemphigoid, and Epidermolysis Bullosa Structural and Growth Defects in Nails Summary Acknowledgments References Chapter 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 How to Evaluate a Model Pathology Terminology, Classification, and Description Genotypes Predict Phenotypes Mouse Comparisons with Human (Table 11.1) Important Techniques for the Evaluation of the Mammary Gland Preparation of Mammary Gland Whole Mounts Preparation of Lung Whole Mounts Fixation and Processing Immunohistochemistry (IHC) Mammary Gland Transplantation Host Response Case Study: 129S6/SvEvTac-Stat1tm1Rds Mammary Biology and Tumorigenesis (Figures 11.2, 11.7, and 11.10) Mammary Growth and Development Summary Internet Resources References Chapter 12 The Respiratory Tract Introduction The Upper Respiratory Tract Anatomy and Histology Developmental Defects Pathology of the Nose The Lung Anatomy and Histology Lung Necropsy and Histology Protocols Immunohistochemistry of the Lung Lung Development Congenital Diaphragmatic Hernia Approaches to Phenotyping the Respiratory System Pathology of the Lung Spontaneous Lung Lesions in Mice Disease Models Scoring of Lung Lesions Infectious Disease Models Mouse Models of Human Pulmonary Genetic Disorders Asthma Pulmonary Fibrosis Models Lung Tumors References Chapter 13 The Gastrointestinal Tract Introduction Stomach Anatomy and Histology Necropsy, Trimming, and Embedding Protocol Pathology of the Human Stomach Pathology of the Mouse Stomach Genetically Engineered Mice Neoplasms and Other Proliferative Lesions Cystic Proliferative Lesions in the Stomach and Intestine The Small and Large Intestine Normal Anatomy and Histology Necropsy and Pathology Protocol Pathology of the Human Intestine Histopathology of the Mouse Intestine Mouse Models of Inflammatory Bowel Diseases and Related Diseases (Colitis Models) Colitis Necropsy and Tumor Histopathology Protocols Microbiota and Colitis Human Intestinal Neoplasia Mouse Models of Intestinal Cancer Intestinal Tumor Pathology Other Intestinal Tumors Specific Intestinal Tumor Models Pitfalls in Interpretation of Intestinal Carcinogenesis References Chapter 14 Cardiovascular System Mouse Anatomy, Histology, and Physiology Heart Cardiac Conduction System Resident Immune Cells of the Heart Circulatory System: Vasculature Elastic Arteries Muscular Arteries and Veins Special Necropsy Organ Protocols Detection of miRNAs of Cardiovascular System Aging/Spontaneous Strain Specific Lesions Osseous Metaplasia (Os Cordis) Polyarteritis Nodosa Epicardial/Myocardial Mineralization Atrial Thrombosis Hyaline Arteriolosclerosis Myxomatous Degeneration of the Cardiac Valves (Endocardiosis) Bicuspid Aortic Valve (BAV) Melanosis Aortitis Opportunistic Bacteremia/Endocarditis/Myocarditis in Immune-Incompetent Mice Neoplasia Genetically Engineered Mice (GEMs) Models of Heart and Vessel Disease Septation Aortic Stenosis Cardiomyopathies Hypertrophic Cardiomyopathy Dilated Cardiomyopathy Arrhythmogenic Cardiomyopathy Other Cardiomyopathies Restrictive Cardiomyopathies Lysosomal Storage Diseases Markers of Cardiovascular Disease in Other Organs Aorta Aneurysm and Dissection Tortuosity Systemic hypertension Vasculitis Atherosclerosis Summary Acknowledgments References Chapter 15 Liver and Pancreas Liver Anatomy, Histology, and Physiology Special Necropsy Organ Protocols Aging/Spontaneous Strain Specific Lesions Genetically Engineered Mice (GEM) Genetically Engineered Mouse Models for Liver Diseases Mouse Models of Nonneoplastic Liver Diseases Histogenesis of HCC and Other Hepatic Tumors Induction of Mouse Liver Tumors Pathways to Human HCC Humanized Mouse Liver Models for Liver Diseases Genetically Edited Mouse Models for Liver Disease Exocrine Pancreas Anatomy and Histology Necropsy, Trimming, and Embedding Aging/Spontaneous Strain-Specific Lesions Pathology of the Human Pancreas Neoplasms and Other Proliferative Lesions Familial and Hereditary Pancreatic Cancer Risk Factors of PDAC Genetically Engineered Mice GEM for Inflammatory Lesions of the Pancreas GEM for PDAC References Chapter 16 Neuromuscular System Introduction General Guidelines Tissue Fixation Tissue Samples Histopathology Motor Neurons Peripheral Nerves Neuromuscular Junctions Mechanoreceptors Myocytes References Chapter 17 Endocrine System Overview General Phenotypic Considerations for the Endocrine System Pituitary Gland Anatomy, Histology, and Physiology Special Necropsy Organ Protocols Aging/Spontaneous Strain-Specific Lesions Genetically Engineered Mice Thyroid Gland Anatomy, Histology, and Physiology Special Protocols Aging/Spontaneous Strain-Specific Lesions Genetically Engineered Mice Parathyroid Gland Anatomy, Histology, and Physiology Special Protocols Aging/Spontaneous Strain-Specific Lesions Genetically Engineered Mice Adrenal Gland Anatomy, Histology, and Physiology Special Protocols Aging/Spontaneous Strain-Specific Lesions Genetically Engineered Mice Pancreatic Islets Anatomy, Histology, and Physiology Special Protocols Aging/Spontaneous Strain-Specific Lesions Genetically Engineered Mice Pineal Gland References Chapter 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 Chapter 19 Female Reproductive System Embryology and Normal Anatomy of Organs of the Female Reproductive Tract Embryology Normal Anatomy and Histology Normal Estrous Cycle Changes Biological Characterization of a New Mutation of Female Reproductive Tract Collection of the Female Reproductive Tract Organs (Ovary/Oviduct/Uterus/Uterine Cervix and Vagina) Special Stains for the Ovaries, Uterus, Cervix, and Vagina Spontaneous or Induced Mutant Phenotypes of the Gonads and Receptors Sex Steroid Receptor Deficient Mice Mutants Affecting Pituitary Function Mutants with Defective Steroidogenesis Growth Factor Mutations Mutants with Germ Cell Aplasia Mutants with Changes in Germ Cell Apoptosis Phenotypes of Gonadal Neoplasia Miscellaneous Models with Reproductive Tract Phenotypes Models of Diseases Affecting the Female Reproductive Tract Models of Polycystic Ovarian Syndrome (PCOS) Models of Ovarian Cancer Models of Endometriosis Models of Endometrial Cancer Models of Uterine Fibroids Models of Cervical Cancer Aging/Spontaneous Strain Specific Lesions Acknowledgments References Chapter 20 Male Reproductive System Introduction Male Reproductive System Accessory Sex Glands Anatomy and Histology Special Necropsy and Trimming Protocols Preputial Glands Necropsy and Trimming Protocols Anatomy and Histology Pathology of Preputial Glands Bulbourethral Glands (Cowper’s Glands) Anatomy and Histology Pathology of Bulbourethral Glands Genetically Engineered Mice Ampullary Glands Periurethral Glands (Glands of Littré) Genetically Engineered Mice Seminal Vesicles Anatomy and Histology Pathology of Seminal Vesicles Genetically Engineered Mice Prostate Anatomy and Histology Special Necropsy and Trimming Protocols Special Histochemical Stains and Immunohistochemical Markers Pathology of Prostate Glands Genetically Engineered Mouse Models Epithelial Hyperplasia Mouse Prostatic Intraepithelial Neoplasia (mPIN) Adenocarcinoma Sarcomatoid Carcinoma Neuroendocrine Carcinoma Specific Prostatic Tumor Models Models with Alterations in PTEN/AKT Signaling Models with Alterations in MYC Signaling Models with Alterations in ERG Signaling Models with Alterations in Fibroblast Growth Factor (FGF) Signaling Models with Alterations in Androgen Receptor (AR) Signaling Models with Alterations in TGF-b Signaling Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) Testes and Epididymis Anatomy, Histology, Physiology Special Necropsy and Trimming Protocols Aging and Spontaneous Strain-Specific Lesions Testis Degeneration, Atrophy, and Germ Cell Depletion Tubular Necrosis Miscellaneous Changes Mineralization Amyloid Pigment Mononuclear Aggregates Epididymis Genetically Engineered Mouse Models of Male Infertility Histopathology Classification and Mechanisms of Action Pathology of the Testis in Infertile GEM Seminiferous Tubule Degeneration/Atrophy Spermatogenesis Arrest and Spermiation Defects Multinucleated Spermatids; Symplasts Germ Cell Exfoliation Tubule and Sertoli Cell Vacuolation Tubular Dilation Primary Ciliary Dyskinesia (Immotile Cilia Syndrome) Leydig Cell Abnormalities Pathology of the Epididymis in Infertile GEM Neoplasms of the Testis Sex Cord-Stromal Tumors Leydig Cell Tumors Sertoli Cell Tumors Granulosa Cell Tumors Germ Cell Tumors References Chapter 21 Nervous System Anatomy, Histology, and Physiology Neuroanatomic Localization Necropsy Protocols Histological Artifacts Aging/Spontaneous Strain Specific Lesions Genetically Engineered Mice (GEM) Disease Models: Degenerative Alzheimer’s Disease (AD) Amyloid Plaques/Models of Amyloid Pathology Neurofibrillary Tangles and Neurodegeneration/Models of Tau Pathology Mouse Factors Online Resources Parkinson’s Disease (PD) -Synuclein Models LRRK2 Models Amyotrophic Lateral Sclerosis (ALS) Spinocerebellar Ataxias Huntington’s Disease (HD) Autoimmune Developmental: Epilepsy Traumatic Brain Injury and Post-Traumatic Epilepsy Malformation Neoplasia References Chapter 22 Eye and Ear Anatomy, Histology, and Physiology of the Eye Optic Nerve Lids and Ocular Adnexa Gross Phenotyping Screen Optic Function Evaluations Posterior Eye Examination Photoreceptor Function Evaluations Special Necropsy Organ Protocols Fixation and Decalcification Tissue Processing and Sectioning – Paraffin Embedded Samples Interpretation of Eye Sections Description/Lesions of the: Globe (as a Whole) Ocular Adnexa and Eyelids Anterior Segments Including the Conjunctiva, Cornea, Iris, and Ciliary Body Lens Posterior Segments in Cluing the Vitreous, Choroid, Retina, and Optic Nerve Neoplasia Spontaneous Mutations Associated with Strain-Specific Eye Lesions Genetically Engineered and Mutant Mice (GEMs) Anatomy, Histology, and Physiology of the Ear Phenotyping Screen Gross Necropsy and Trimming Embryology Histology Aging/Spontaneous Strain Specific Lesions Abnormalities in Genetically Engineered Mice Middle Ear Abnormalities Inner Ear Abnormalities Vestibular System Abnormalities References Chapter 23 Bones and Teeth Introduction Bone Bone Structure Bone Cells Differences Between Mouse and Man Phenotyping Mouse Bone Histomorphometry Whole Mounts Dual X-ray Absorptiometry (DXA) Microcomputed Tomography (CT) Additional X-ray-Based Imaging Techniques Biomechanical Testing Histology Diseases of Bone Fibro-osseous Lesions Diseases of High Bone Mass Diseases of Low Bone Mass Biomineralization Defects Osteogenesis Imperfecta Cartilage Defects Teeth Abnormal Tooth Numbers/Shapes Enamel Defects Dentin Defects Incidental Lesions Acknowledgments References Index EULA