Laboratory Rat (eBook)

Front Cover 1
The Laboratory Rat 4
Copyright Page 5
Contents 6
List of Contributors 12
Foreword 16
Preface 18
Part 1: The History and Development of the Rat as a Laboratory Model 20
Chapter 1. History, Strains and Models 22
Introduction 22
Historical Foundations 22
Rat Strains and Stocks 27
Chapter 2. National and International Guidelines for the Conduct of Chemical Safety Studies: Choice of Strains 36
The Rat as an Experimental Animal in Chemical Safety Studies 36
Guidelines for Chemical Safety Studies Using Rats 37
General Recommendations for Safety Studies in the Guidelines 40
Outlines of the Various Safety Studies 42
Considerations 46
Part 2: Housing and Maintenance 48
Chapter 3. Handling and Restraint 50
Introduction 50
Safety 50
Handling and Restraint of the Rat 51
In Summary 61
Chapter 4. Husbandry 64
Introduction 64
Microenvironment and Macroenvironment 64
Cage Cleaning 70
Identification 71
Enrichment 72
Chapter 5. Nutrition 76
Introduction 76
Factors Affecting Nutrient Requirements 76
Nutritional Requirements 78
Type and Form of Diet 84
The Need to Control Dietary Intake 84
Dietary Control of the Adverse Effects of AL Overnutrition 90
Conclusion: The Need for Nutritional Control 91
Chapter 6. Animal Welfare Laws and Regulations 96
Introduction 96
Overall Structures and Frameworks 98
The Work 100
The Facilities 106
The People 109
The Administration 111
Conclusion 111
Further Reading 113
Part 3: Rat Pathogens 116
Chapter 7. Common Diseases 118
Introduction 118
Viral Diseases 118
Bacterial and Mycoplasmal Diseases 130
Parasitic Diseases 143
Chapter 8. Control of SPF Conditions: FELASA Standards 152
Introduction 152
Definition of 'SPF' 152
Requirements for Housing 'SPF' Animals 153
Risk Factors 154
Health Monitoring Programme 155
Health Report 159
Part 4: Reproduction and Breeding 162
Chapter 9. Physiology of Reproduction 164
Introduction 164
Sexual Differentiation 164
Puberty 167
Spermatogenesis and Testicular Functions 169
Estrous Cycle 171
Pregnancy and Parturition 182
Embryo and Fetus 185
Lactation 186
Reproductive Behavior 190
Chapter 10. Breeding and Assisted Reproduction Techniques 196
Introduction 196
Inbred Strains 197
Co-isogenic Strains 199
Congenic Strains 199
Segregating Inbred Strains 202
Hybrids 202
Recombinant Inbred Strains 203
Outbred Stocks 204
Embryo Transfer 208
Storage of Rat Strains as Frozen Preimplantation Embryos 214
In Vitro Fertilization (IVF) 215
Chapter 11. Reproductive and Developmental Toxicology Safety Studies 218
Choice of Species and Strains 218
Definitions 219
Regulatory Requirements for Reproductive Toxicology 219
Routes of Administration 224
Selection of Dose Levels 224
Animal Supply and Husbandry 227
Treatment of Controls 227
Embryotoxicity or Prenatal Development Studies 228
Fertility and Postnatal Investigations 232
Reporting of Data from Reproductive Toxicology Studies 239
Chapter 12. Developmental Neurotoxicity 246
Introduction 246
The Value of Experimental Animal Data 246
Vulnerability– Some Fundamental Differences between the Developing and the Adult Nervous Systems 247
Developmental Stages and Critical (Vulnerable) Periods in the Development of the Nervous System – an Anatomical Approach 252
Developmental Stages and Critical (Vulnerable) Periods of the Development of the Nervous System– a Cellular Approach 254
Developmental Neurotoxicity Studies in Rats 261
Part 5: Anatomy 270
Chapter 13. Gross Anatomy 272
Introduction 272
Chapter 14. Imaging 296
Introduction 296
Chapter 15. Synopsis of the Organ Anatomy 302
Introduction 302
Part 6: Physiology 340
Chapter 16. Respiration 342
Introduction 342
Structural Features 342
Respiratory Mechanics 345
Ventilation of the Lung 348
Aging of the Lung 350
Particle Deposition in the Respiratory System 350
Particle Clearance from the Respiratory System 352
Airway Reactivity 354
Exposure Methods in Regulatory Toxicology 355
Chapter 17. Circulation 364
Anatomical Heterogeneity of Blood Vessels 364
Physiology of the Blood Vessels 365
Physiology of the Heart 368
Pathophysiology in Hypertension 369
Chapter 18. Digestion, Metabolism 378
Digestion 378
Metabolism 390
Chapter 19. The Urinary System 404
Introduction 404
Basic Anatomical Considerations 405
Vascularization of the Rat Kidney and Regulation of Renal Blood Flow 406
Glomerular Structure and Mechanisms of Glomerular Filtration 410
Cortical Peritubular Microcirculation and Fluid Reabsorption 412
Juxtaglomerular Apparatus (JGA) and Tubuloglomerular Feedback (TGF) 413
Tubular Structure and Function 413
Other Functions of the Rat Kidney 417
Practical Urinary Collection and Analysis 418
Chapter 20. Endocrinology 420
Introduction 420
Hypothalamus 420
Pituitary 422
Testis and Ovary 425
Uterus 427
Placenta 428
Heart 428
Adipose Tissue 429
Thyroid Gland 429
Parathyroid Gland 430
Adrenal Gland 430
Kidney 431
Pineal Gland 431
Pancreas 432
Gastrointestinal Hormones 433
Chapter 21. Behavior, Neurology and Electrophysiology 438
General Aspects 438
Clinical Approach 439
Neurological Examination 441
Neurophysiological Techniques 445
Ethological Approach 447
Behavioural Tests 448
Conditioned Behaviour 448
Regulatory Neurotoxicology 452
Chapter 22. Immunology and Hematology 456
Immunology 456
Hematology 458
Chapter 23. Physiology of Stress and Starvation-like Conditions 466
Stress 466
Starvation-like Conditions 473
Part 7: Procedures 480
Chapter 24. Routes of Administration 482
General 482
Principles of Administration 483
Enteral Administration 484
Parenteral Administration 489
Other Methods for Parenteral Administration 498
Chapter 25. Collection of Body Fluids 504
Blood 504
Urine 513
Lacrimal Fluid 517
Saliva 517
Peritoneal Fluids 517
Bile 518
Pancreatic Juice 519
Semen 520
Female Reproductive Products 522
Milk 523
Lymph 524
Cerebrospinal Fluid (CSF) 525
Chapter 26. Anesthesia, Artificial Ventilation and Perfusion Fixation 530
Anesthesia 530
Artificial Ventilation 535
Perfusion Fixation 537
Chapter 27. Experimental Surgery 542
General Principles 542
General Techniques 545
Permanent Cannulation of the Jugular Vein 549
Permanent Double Bile Fistula with Intact Enterohepatic Circulation 552
Permanent Cannulation of the Portal Vein 557
Permanent Cannulation of the Iliolumbar Artery 560
Transplantation of the Heart 562
Orthotopic Lung Transplantation 566
Intracranial Surgery 570
Basic Surgical Procedures 579
Chapter 28. Necropsy Techniques with Standard Collection and Trimming of Tissues 588
Introduction 588
Necropsy Preparation 589
Trimming of Fixed Tissues for Processing 606
Part 8: Emerging New Techniques 620
Chapter 29. Genetic Engineering and Molecular Technology 622
Overview: Use of Genetic Methods in Vertebrate Biology 622
Tools for Exploring Interesting Genes 623
The Rat as a Species of Choice for Genetic Engineering 624
Genetic Manipulation of Rats 625
Genotypic Analysis of Engineered Rats – Detection of Gene Insertion 647
Phenotypic Analysis of Engineered Rats 647
Appendix 1: Table of Genetic Markers in The Rat 654
Appendix 2: List of equipment suppliers/vendors by country 744
Appendix 3: Societies Active in Laboratory Animal Science 748
Glossary: (Terms defined in the glossary are emboldened in the main text) 750
Index 756
Color Plate Section 289