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