List of Contributors ................................................................................................................................................................................................. x\ .

Foreword ................................................................................................................................................................................................ xix

Preface ................................................................................................................................................................................................................ xxi

Part 1 History and Genetics

Chapter 1.1 Origins and Phylogenetic Relationships of the Laboratory Mouse . Jean.l.nuis C&nel. Ann& Chth and Francois Acmhom~w - ......................................................................... . 3

Introduction .....-.....-....-.- " - ................................................................................................................ 3 6 ....... z Phylagenetic relationships of the house mouse - ................................................................................................ 4 ;;I The house mouse as a laboratory model: a historical perspective .....-......-....- . .................................... . 9 z The house mouse and its wild relatives ........................ "- ...................................................................................... - 13

J . References .-............. ..-. ................................................................................................................................................ 15

Internet resources . ................................................ . ................................................................................................... 20

Chapter 1.2 Historical Foundations -- &mi C . I. in& and M u d T . Davi~.son ..-........ ". ....................................... .. 21 Introduction ..... "- ........................................................................................................................................ - 21 1902-1940: the birth of mouse genetics - ....-......- . ............................................................................... 23

1941-1960: discovery and expansion of mouse resources ...--.....-- ..... ................................................................... 25 1961-1980: mapping the mouse genome .-- ....-..... " ....................................................................................... . 25

1981-2000: genetic mapping advances and manipulation of the mouse genome .................................. 27 2001-2011: the mouse genome sequence and beyond ...- .....,.-.....-...... " ................................................................. 30

Acknowledgements - .......................................................................................................... 31 References , ................................................................................................. . ............................................. ........................... 31

Chapter 1.3 Strains. Stocks and Mutant Mice . C a l h h M . L.uL.z, Carol C . Lb& and Mulie1 7: Davisson ............................................................... 37

Introdr~ction .............................................................................................................. .. "- .. .................................. 37

Stocks and strains - .......-....--.-.-...... - ...... ...................................................................................................................... 38 Inbred strains .... - ............................... " .................................................................................................................. 38 Hybrid mice ............................................. "- ............... "....--.....-"...-w...-...--......u-..............-.....-....-......."...-.....--.........-..-........"...-. 41

Traditional outbred stocks - ....--......,.........--.......-.....--.....-..--....-w.........--....-........ " ................................. ".--...-...".-... ". 42

Wild-derived inbred strains , ..................................................................................................................... 42

Mice with chromosonlal aberrations -" ... ".-.--.- ................................................................................... 43

..... Congenic strains ........................................................................................................ " ...-.....-....--.... "-..-."..-....-...-.-. 44

Recombinant inbred swains. reconlbinant congenic strains and advanced intercross lines .......................... 46

The Collaborative Cross ...................................................................................................................................................... 47

Mutant mice: sponlaneous mutations. transgenes and targeted mutations ....................... "- ............................ . . 48

References ............................ "- ....---.............. ................................................................................................................................................. 53

Chapter 1.4 Mouse Genomics -- h 7 t a n h J . Bmavldes crnd Jean-huu G ~ P I - ...................................................... 57

Introduction ....................................................................................................................................................................... 57

Structure of the mouse genome ................................................................................................................................................... 58

Functional annotation of the mouse genome ................................................................................................. .................... 70

References .-. ................................... ................................................................................................................................................ 82

Relevant URLs for mouse genomics ................................................................................................................................ 90

Chapter 1.5 Generation of Mouse Mutants by Genotype-Driven Mutagenesis . Thomas Rtilicke .-...,- .....-....-....-...... . ...................................................................................... 91

Introduction ..-. ...........-. . ....................................................................................................................... . 91

Transgenic animals-a definition ................................................................................................ 92

Methods for additive transgenesis by random integration ...-- ............................................ . 92 Transgenesis by targeted mutation using embryonic stem cells ,. .......................... . . . 97 Advanced methods of transgenesis .................................................................................. 101

Fluorescence reporter in transgenic mice ....................... - .- ............................................................ . 104

Perspective ..-....-....-...-....-- . .............................. . - ....-. ........ .......................... . ...-....-... ....................... -- 106

References .-.....-....-, ............. ............................................................................................................. 107

Part 2 Anatomy and Normative Biology

Chapter 2.1 Early Mouse Development -- Andreas Kispot ram1 Aehim Gossler .. ........................................... . 117 Introduction ..-.........-.. .- ...... ...................................................................................................................... 117 Fertilization and preimpbntation development .-. ..--....--..,...-...,.. .., ............................. . 117 Early postimplantation development ............................................................................. . 123

Late embryonic development: completion of organogenesis and fetal growth ..- ................................ 135

References ........................... .... ..... .-...- ...................................................................................... I36

Chapter 2.2 Gross Anatomy -- Viiuiimir Korndrek ......................................................................................................... . 145

Introduction ........................................................................ ".- ....."......-- ............................................................................. 145

Acknowledgement .............................................................................................................................................. I59

References 159

Chapter 2.3 Histology -- C d q J . Krinke nnd Klaw W e k .. ................................. . ....................................................................... "... 161

Introduction ........................... .. ............................................................................................................................ 161

Cardiovascular system ........................................................................................................................................................... - 161

Digestive system .............................................. . .................................... .............................................................................................. - 163

Gallbladder .................................................................................................................................................................................. 163

Endocrine system ............................................................................................................................................................. 170

Genital system ..................................................................................................................................................................... 172

Haematopoietic and lymphoreticular system ................................................................................................................. 178

Musculoskeletal system ....................................................................................................................................................... 180

Nervous system .- ...................................................................................................................................................................... -. I81

Respiratory system ......................... ". ............................................................................................................................ 183

Sensory organs and adnexa ............................... ., .................................................................................................... 185

Skin and mammary glands ............................................................................................. ". ...-........... ............................... 187

Urinary system ................................ "- .................................................. 188

Most common strain differences in the occurrence of age-related changes ....................................... 2 References ............................................................................................................................... ".. .................................... 191

General information ............................................................................................................................................................. I92

Chapter 2.4 Skin and Adnexa of the Laboratory Mouse . John P . Sundbetg. Chrklopher S . Palter and Lloyd E Kzng. Jr .- .......................... - ................................. I93

Introduction -.. ....................................................................................................................................................................... I93

Clinical evaluation, tissue collection, and preservation of the skin - 194

Developmenr of the normal skin and adnexa .............................................................................................. 200

Normal anatomy of the skin and the hair cycle ................................................................................ ".- .................. 201

Nails ........................... .. ........................................................................................................................................ 203

Other specialized glands .................................................................. " .................................... ............................................... 204

Skin and adnexal mutant phenotypes ....-..l......-.......-.....-.....-.........-.....u....--.......v.-....-..-...... " .............................. "....... 204

References ................................................................................................ ".- .................................................... "............."-.... 204

Chapter 2.5 Development and Disease of Mouse Muscular and Skeletal Systems . Roger B . Skr . Gresny A . Cdx and C h y l A&-BlckneLL ................................................................ -- - ... 209

Part A . Muscle systems ..-- ........................................................................................ " ......................................... 209

Introduction ................................................. "- ............................................................. ........................................ 209

Cellular and molecular development - ......--...-.., " ...,-.... ........................................................................................ 210

Fetal muscle development ............... ................................................................................................................... 212

Adult muscle function ........................................ " ............................................................................................................... 215

Degenerative diseases and genetic models ..................................... . ............................. ........................................ 217

Part B . Skeletal systems .................................................................................................................................... 220

Lntroduction ...........-.....-. . .................................................................. .............................................................................. 220

Bone anatomy and composition ...-....".........-.. . .................................... ......l..-......l.......e.............l...... 221

Bone cells ." ..............-,... "...-....... - .- ........................................................................................................ 221

Embryonic origin of bone ........................................................................... " ............................................................... 229

Bone remodelling 230

Bone and energy metabolism ......- " ... ................................................................................. " ..................................................... 230

Summary ................................................................................................................................................................... 231

References ................................................................................................................................................... 231

Chapter 2.6 The Cardiovascular System . Lloyd H . IMK~UPL. Gwge E . T~flei. hiark 1- Enlmon. Antlkumar K . Reddy. Crarg J . Hart@ and Nikolaos G . Franpgiannzs ....... + ...................................... ........ ...................... 241

Introduction ................................................................................................................................................. 24 I

Anatom~cal considerations .......................................................................................................................................... 242

Histopathological characteristics of the normal mouse heart .......................................... . 243

Mouse electrocardiography - ..... .., ............................................................................................................................................... 245

Functional cardiovascular measurements in the mouse-invasive versus non-invasive ...................... 247

Experimental models .................................................................... "- ...................................................... .. 255

Pathology of myocardial infarction in mice ......................................... " .................................................................. 256

Pathology of myocardial hypertrophy - ......................................... ............................................................................. 260

Murine models of cardiac fibrosis ........................................................................................................................... 260

Cmngestive heart failure .................................................................................................................................. 262

Murine models in aortic disease ....................................................................................................................... 264

Acknowledgements .- ............... ..-.. ................. .................................................................................................................. 264

References ............................................................................... "- ............................................................. .................................. 264

Chapter 2.7 The Respiratory Tract . Armirt Braun. Hanmh Eml. Utrk Srhawtza. Heznz-Ckrd Hqymantz. attd Susanne Ruinghcitnoz ............. 271

Introdr~ction ....................................................................................................................................................................... 2'71

Anatomy and normal structure of the mouse lung ....................................................... "- ................................. . 272

Immunology of the lung .- .... "- ............................................................ ................................................................................ 272

Physiology of the lung ....................................................................... " ...................... ............................................................... 273

Lung diseases and pathology ........................ . .............................................. " ................................................... "-........ ". 280

Non-neoplastic lesions ...............-.-... ". " ..- ........................................................................................................................ 283

T~~nlours of the respiratory system .....- " .......-.-......-... .I, ............................................................................... 289

Murine models of lung cancer ........................................................ " ...................................... ............................... 2% Conclusion ............................................................. .-- ..... ............................................................................................................ 303

References ...-......-.....-.. . ...................................................................................................................................... . 303

Chapter 2.8 The Gastrointestinal System and Metabolism -- Carolyn D . Mdnnwr ................................................. 713

Introduction .................................................................................................................................................................... 313

Digestive system .. ...................................................... . ....................................................................................................................... 313

Endocrine aspecLs of digestion and absorption I ....................................................................................................... . ....*....... 318

Metabolism ....................................................................................................................................................................................................... 318

References ....... - . ....-........ " .. .- .................................................................................................................................................... 328

Chapter 2.9 Haematology of the Mouse -- Anne Pmvmchrr BoUiger and Nancy Evmds ...................................................... 331

Introduction ....................................................................................................................................................................... 331

Terminology .................................................................................................................................................................... 331

Blood collection and handling ........................................................................................................................ 332

Basics of haematological evaluation . 332

Variables affecting haematology results ................................................................................................................... 339

Pathophysiology and interpretation of results ..-...... -"- ................................. .............................................................. 340

Bone marrow evaluation ...... "" .... 345

References ................................................................................................................................................ - 345

Further reading -- ......-"....--.. ... ....................................................................................................... 346

Chapter 2.10 Studying Immunology in Mice -- Mnrih.d Alnm and Wenzer M& ......... ...-.......... .......................... ....-.... 349

Introduction ............................................................................ -.- ....................................... .......................................................... 349

Dependence of immune system status on microflora and other microorganisms .................................. . 350

Dependence of the immune system on he genetic background ..................................... . . 351

The 'mouse trap', or why the mouse is needed in immunology ................................. ................................................ 352

Using in ailro systems to replace animal experimentation ............................................................................... - 358

Humanized mice ...................... .. ........................................................................................................................... 360

Concl~~sions ....... - - ..................................................................................................................................................... . 362

References - ....................................... ".- ....................... .................................................................................................................... - 362

Chapter 2.11 The Behaviour of the House Mouse -- Barbaru K0nlg ...... " ........................................................................ %7

Introduction . ................................ - . ............................................................................................................. 367

Taxonomy and biogeography of the ho~lse mouse -- ....................................................................................... 767

The house mouse m research ...................................................................................................................... 368 Behavior~ral flexibility in the western house mouse ............................................................................................ 368

Flexibility in maternal reproductive strategies ............................................................................................................... 371

References ...........-..-..-... " ............................................................................................................................... 376

Chapter 2.12 Biological Rhythms of the Mouse -- SiPphnn Skinkrhntr .....-.-........Y .̂...w.....................-........q......-..............-...... %3

Introd~tction ..- - ..... ............................................................................................................................................... 383

The biological clock .................................................................................................... ..- ........................................... ".. 384

Formal properties of endogenous clocks - .................................................................................................... . 385

Anatomical structures and components of the biological clock ............................................................. 389

The cellular clockwork - ..-......... "" ............................... ................................................................................................. 391

Peripheral clocks slaves to d ~ e master clock? ........................................................................................ 394

Phenotypic effects of mutations in circadian clock genes -.- 397

Practical recommendations from the viewpoint of chronobiology ., .....-.... .- .......................................... 399

Conclusion ............... .................................................................................................................................................. 400

References ......-.......... ... .............................................................................................................................................................. 401

Part 3 Neoplasms and Infectious Diseases

Chapter 3.1 Diversity of Spontaneous Neoplasms in Commonly Used Inbred Strains of Laboratory Mice . Dale Reg& Beth A . Sundbog, Annerose Bmdt . Janan @pig. Paul N . Schofield and John 1'. Sunrlbmg, .......-...... .- .................................................................................................................. 41 1

Introduction ..- .......................... ................................................................................................................................................. 412

The mouse tumor biology database and pathbase ....................................... 413 Strains ...-..... ....--........... "... .. ..................................................................................................................... " ....................................... 414

Other large-scale ageing studies using mice ..-....-..-.........-.. ". ............................................................................... 414

Mouse cancer websites ..............-..... " .................................................................................................................................. 423

Acknowledgements - .............................................................................................................................................. - 424 n References -.- .................................................. ........................................................................................................................... 424 0- .. .. z

;;I Chapter 3.2 Viral Infections of Laboratory Mice - f

W m r N i r k h . Andri BlPiclt and Michnel Mahler .................................................................................. 427 iz Introduction ..................................................................................................................................................... 427

DNA viruses ................................................................................................................................................... 429

RNA viruses ........................... - ......................................................................................................... 442

References ....................................................................................................................................... 461

Chapter 3.3 Bacterial Infections of Laboratory Mice . Charles B . Claflwd and Kalhlemz K Pri&he~-Coning ..-...-....-...-...... ... A L

Introduction ......................................................................................................... . .............................. 481

Gram-positive bacteria ................. ................................................................................................. 483

Gram-negative bacteria ..................................................................... . .......................................... <..-.......- 490

. References .......-.......-...-. ..-.-.....- ............................................................................... 497

Chapter 3.4 Parasitic Infections of Laboratory Mice . Kalhlm R A'&hL.rf.Carning and Charles B . Cltffwd ... ........................................................... - 503

Introduction .. ....-..-..-.......... . ................................................................................................. . 503

Internal parasites of laboratory mice .............................................................................................. 504

External parasites of laboratory mice . ................................ . ....................................................... 512 References -- .................................................................................................... 515

Part 4 Husbandry and Maintenance

Chapter 4.1 Housing and Maintenance -- Ham Jiitgen Hedrich and Werner Nickh ......... .- .................................. . 521

Introduction -. ............................................................ . ................................................................................................... 521

General aspects . ............................................................................................................................ . 521

Hygienic characteristics of laboratory mice .....-. .., ................................................................................ 524

Housing s y s t e m . ............................................................................................... ....- .....-....-...-....... 525

Housing conditions for specific purposes .- ......................... . ....-... . ..................................... 532

Infected animals and infection experiments .- .................................................................................. 533

Refinement of housing and environmental enrichment .- ........................................................................ . 535

Therapeutic treatment - ............................................................................................. 536

Identification systems .- ....-..-.---.- .................................................................................................... . 536

Computer-assisted management of animal facilities ...................................................................... 538

References - ......................................................................................................................................... 539

Chapter 4.2 Mouse Enrichment -- Kathryn B a y and Hanno Wii&-1 .......................... -.I ............................ 547

Introduction . ........-. . ............................................................................ .................................................................... - 547

Implementing environmental enrichment ............................................................................................. 548

Effects of enrichment ............................. .... ..- ...-....... " ............................................... .............................................. 554

Assessing the value of enrichment - ...................................................................................................... - 559

Keeping mouse enrichment practical .- ...-.....-..... - - ........ - ... "- ..... - ...-.... - .- ............................................................. 560

Conclusions .-." ..-....-.....-"...-... - - ............................ "- .....-... ............................................................................. 561

References .-. ". " .............................................................................................................................. . 561

Chapter 4.3 Nutrition of the Laboratory Mouse . . Mere1 kIsh.Hottmngu, Graham l'obzn. Tanja Lyholm Jmren and Lars Fritr MlkkeLren ...................... ............ 567

Introduction - .................................................................................................................................... 567

Nutritional requirements ..................--.- " ....--.... - .- ......................................................................................... 568

Types of diets .......................... . .............................................. ................................................................................................... 575 . .

Storage condiuons .......................................................................................................................... 577

Pellet hardness - ................................................ . .................................................................................................. 578

Autoclaving/irradiation .-.. ...-.... .-- ................................................................................................................. 578

Quality control ...-...........-..... "-.- .......................................................................................................................................... . 578

Ad ltbttum feeding versus food restriction .- ......".......... .., ........................... 579

Pair feeding .................................................................................................................................. 580

Normal feeding behaviour versus food restriction .. ................................................................................ 580

Individual housing versus group housing ..................................... -. ................................................... 582

Isocaloric exchange ..-..-....--. ".- ............................................................................................................ 582

Mouse models in nutrition research .-..,. .................................................................................................... . 583

Fasting .................................................................................................................................. 589

Welfare considerations and enrichment ............................................ " ......--.....---...-..-..-......m-............-........-.......-.. 589

References -.- ....--..-....- .".-.-.-.- ...................................................................................................................... - 593

Chapter 4.4 Health Management and Monitoring -- MvhaelM~hkr and W m N i c k -. ...... ..., ..................... "601

Introduction .................................................................................................................................................... 601

Significance of infectious agents ............................... . .............................................................................. .. 601

Definitions of microbiological status .....-...-.-....-... . - ..................... . 603

Sources of infections .. ........................................................................................................................ - 604

Health monitoring programme ............................ .. ..- - 607

Health report .......................... . ......................................................................................................................... 615

References ...-............--. . .................................................................................................................................................... 617

Chapter 4.5 Genetic Monitoring of Inbred Strains of Mice . Dirk Wed~kznd. Kurt Reiienbq and Ham J u r p Hdrich ................................................................... 621

Introduction - ................................................................................................................................................. 621

Inbred strains .- .......................... . ........................................................................................ 622

Factors that compromise genetic quality of inbred strains ............................................................ - 623

Maintenance of inbred strains . ...-...-...-......-... .., ............................................................ - 624

Principles and strategies of genetic monitoring .......-....--.-..-......... . ........................................... 628

Marker systems and strategies for genetic monitoring of inbred strains ............................... .......... 633

References .......................... .., ..,.. - . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635

Chapter 4.6 Gnotobiology and Breeding Techniques -- Pahick Hardy ..... ................................................... 639

Gnotobiology .................................................................................................................. 639

Health standards definitions and categories ....................... ., .....-.... ..- .. ................................................. 640

Breeding techniques .- ........................... . ......................................................................... 658

Mating systems and breeding techniques ...................... . - ......................................................... . 666

References ...................... ., .................................................................................................. . ...................... 670

Chapter 4.7 Cryopreservation of Preimplantation Embryos and Gametes. and Associated Methods - M U I I ~ ~ L U M u m 1)ot~rh ..-......... . ................................................................................. 67.5

Introduction .................................................................................................. ".- ............................................................... "."..........-.... 675

Cryopreservation o l epididymal sperm .......................................................................................................................... 676

Cryopreservation of preimplantation mouse embryos - .......................................................... ............................... 678

Cryopreservation of oocytes .- ............................................................................................................................. ... 681 Cryopreservation of ovaries . ....................................................................................................................................... 682

Setting up frozen storage of mouse germplasm ... ........-........-. - .................................................................... 683

Associated methads for cryopreservation .................................................................................................................... 685

Miscellaneous .. ................................................. ....... ". ...... ............................................................................................................... . 691

References ............................................................................................................................................................. . 692

Part 5 Procedures

Chapter 5.1 Handling and Restraint -- Ti& W i s and Thomas Riirge .....-..... " .................................................................. 697

Occupational health and risks ....................................................................................................................................... 698

Definitions ...-......--...... ................................................................................................................................. 699

Handling techniques ..-...-...."....... ..... - .................................................................................................................................. 699

Transfer of mice .......................... . .................................................................................................................................................. 699

Effect of handling and restraint on well-being of mice ............................................................................................. 706

Summary and recommendations - ........................................................................................ -- .................................................. 707

References ..................................................................................................................................................................... - 707

Chapter 5.2 Routes of Administration -$m Hlrola and Shinya Shtmw ti. .....--....-...... .., - ...... ....l ...... - .................................. 709

Introduction - ....--..- ......-..... . ........................... . . . ...-. . . ........................ .. ............................... 709

Principles of administration .- ................................... "- .......................................................................................................... 710

Needles and syringes .- ..................................................................................................................................................... . 714 . . .

Enteral adm~n~s t ra t~on .................................................................................................... . ................................. 715

Parenteral administration ............ - ................................ . .................................................................................................................. 716

Subcutaneous administration .................................................................... ".... ................................................................................ 716

Intraperitoneal administration ......... ........................................................................................................................ 717

Intravenous administration ............... ". ...........-. .....- ............................................. ".-. ......................................... "...-......... 718

Intramuscular administration ................................................................................................................................... 719

Intradermal administration ...................................................................................................................................................... 719

Intracerebral administration - .................................................................. 720

Intrathoracic administration ...................................... "- ...................................................... 721

Lntranasal administration ........................................................................................ 721

Topical application - ................................................................................................. "- ..."..--.-.".-....--... 721

Inhalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7'21

Other routes - ...........--.-.-.-----...---...-.-....-....--..-.--..-..-ww.--...-.....---. " ...-....--...---.-- "....-..--.- 722

Implantable pumps, controlled-release drug delivery pellets and cannulas ..................................... - 722

Immunization ..-......-....-. " ....-. ~-.--..-.-.....--...-.--.....---.u-....-..-....-.....--...~..v......-......-...-......-.u..-...~....--- 722

Rescue from anaphylaxis ............................................................................ 723

Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . - 723

References - ................................................................................................................................ 723

Suppliers' websites - .....-"....-"....----... " ................................................................................ 725

Chapter 5.3 Collection of Body Fluids -- Katsuhim Fuhwa- ................................. . -.. ........................................................ 727

. Blood ., ....-....-.....,,.... .., .......................................................................................................................... 727

Urine ................................ . ...-.--...... " .................................................................... ................................................... 733

Milk ...- .....-.......-... .. .... - ...... ..- ........................................................................................................................ 735

Bile - .................................................................................... . A .................................................................. . . 736

Semen ..-.... A ...,-....,....-.. . ....................................................................................................................... 737

Saliva ..................................................... .. ............................................................................................................... 737

Lacrimal fluid .....-..-.-...-. ...... .. ......-............ .a. ......................................................................... -.. .... 737

........... ...... ................... Peritoneal fluids - ....-...-..- -"- - .I .....- ....................................................................... 737

References ....................... . ....-....-........-. ..- .............................................................................................. . 738

Chapter 5.4 Anaesthesia, Analgesia and Euthanasia .

Klaus Otto and AnneKathn'n uon Thaden .........-..-,... . ..-........... ..- ........................................... 739

Introduction ................................................................................................................................... .. 739

Anaesthesia ..., ........................................ .- ....................... ............ .................................................... 739

Analgesia .......................... . .................................................................................................................... . 752

Euthanasia .............................................................................................................. 754

. References ., ....--.-.-......... .. ......................................................................................... 755

Chapter 5.5 Imaging the Laboratory Mouse in uivo .

Deanne Lisle; Wilbur R LeopoU and Patrick McCmutlle ...................................................................... 761

Introduction ............................. - - ........................................................................................................ 761

Mouse imaging: why the fuss? - ...--....-.-.u..-......-....--.....-.-...~-....-..~...-...--.......-.-u....-..............-.....-...--..-...u.-.... 762

Mouse imaging: the technology who's who .- ...................................................................................... 762

Facilitating mouse modelling of human disease and therapeutic development through imaging ....... 767

Spectroscopy and spectroscopic imaging ......... " .....---... . .............................................................................. " . - 772

The future of mouse imaging ..................................................... "-.-.- "-....--.....-.-...-.....- 772

Summary - -" ................................................................................................................ - 774

References .................................................................................................................. 774

Chapter 5.6 Necropsy Methods -- KarhlPPn A . Stlun and John I-'. .Szcno%erg. ..................................................................... 781

....... ............... Introduction ..-.....-...... - -. .- "- ..-....--.....-........- ............................................................................................ 781 .............. Biological characterization of a new mutation -" ....,...--....--.... .- ................................. - 781

Clinical evaluation ....................................... "- ....................... ....................................................... 783 Clinical pathology ... " .... .......................................................... . ...................................................... 784

Gross pathological exammation ............................................. "- .. .................................................................... 785

. Fixatives ........ ................................................................................................................................................ 785

. Euthanasia ......................................................................................... ". ..................................................................... 786

Necropsy procedure .................................................................................................................... 790 . .

Trimm~ng tlssues for histology .., " ........-....-.-...-.. ............................................................................................. 796

Routine histological staining .- ..................................................................................................... 803

Conclusions .-.-, .... - ....... "-me- ................................. ....................................................................................... 803

Acknowledgements ..... , - ................................ . ....................................................................... 803

Appendix: examples of commonly used fixatives for mouse histopathology - ..--...-....-.-.- " ...-.-..-. 804

References , ........................................................................................... . .......................... "- ..............--... - .. 806

Part 6 Legal Regulations

Chapter 6.1 Laws. Guidelines and Policies Governing the Use of Mice in Research - Judy A . MarArthur Clccrk and Joanna Zurln ............................................................................... 811

Introduction ..,.... . ......................................................................................................................................................... 811

..... General principles ........................................................................................................ 8 1 1

Regulations especially relevant to laboratory mice , ....................... ...... ., ............................................................... . 817

Regional laws, guidelines and policies ........................................................................ " .................................... ".. 818

Acknowledgements .,.-.- ............................................................................................................. .. 825

References .................................. . ............................................................................................................... 825

Index ....................................................................................................................................................................................................... 831