Genetically Engineered Mice Handbook (Research Methods For Mutant Mice)

✍ Scribed by John P. Sundberg, Tsutomu Ichiki

• Publisher: CRC Press
• Year: 2005
• Tongue: English
• Leaves: 337
• Series: Research Methods For Mutant Mice
• Edition: 1
• Category: Library

✦ Synopsis

While mice have always been highly popular laboratory subjects, their suitability for genetic engineering has solidified their position as today's lab animal model of choice. However, their increased use in genetic studies has created a demand for input on phenotyping that is not always easily met.

To improve the flow of information on the pathology of mice with spontaneous or genetically engineered mutations, prominent researchers organized a series of meetings. Recognizing other needs, the organizers gradually broadened their focus, until finally they expanded to provide an overview of the entire field of genetically engineered models.

The Genetically Engineered Mice Handbook is an extension of those meetings. It offers an introduction for those entering into this area of research, while also serving as a resource for those presently employing mice as laboratory models. Highly comprehensive, this volume covers pertinent aspects of genetically engineered mice, including the use of models for developmental biology and the monitoring of laboratory colonies. With contributions from nearly five-dozen leading researchers, the text presents systematic approaches for analyzing mutant mice for specific medical applications, details a variety of methods for creating mutants and includes information that is particularly hard to access dealing with legal responsibilities.

This essential reference examines commonly used traditional, as well as emerging, technologies To address the purpose of the original meeting, the Genetically Engineered Mice Handbook directs researchers to the best public websites, and offers instruction on how to use them. In the past, as their work dictated, researchers would seek out experts on particular organ systems. Now groups of experts work together to generate these websites, providing the latest data as well as discussions over points of debate. These sites do not eliminate the need for a trained pathologist, but they do provide reference materials for those lacking expertise in particular anatomic structures. They also offer much greater numbers of examples than are available in print, from which biomedical researchers can draw.

Features: · Summarizes commonly used and emerging technologies to bring beginners up to speed · Provides key URL's to access relevant public databases, with instructions in many languages · Details specific microflora needed to optimize experimental results, while also listing those agents which can negatively impact experiments · Examines new approaches used to generate repositories of embryonic stem cells that carry null mutations with reporter constructs · Includes comprehensive information on basic issues of modern mouse biology and husbandry · Contains a 12-page full-color insert to enhance detailed understanding

✦ Table of Contents

Preface......Page 8
Editors......Page 10
Contributors......Page 12
Table of Contents......Page 16
Generation of Mutant Mice......Page 20
Maintenance and Archiving......Page 22
Phenotyping Approaches......Page 23
References......Page 24
Sharing Research Tools: The Laboratory Mouse......Page 30
1980......Page 31
Cold Spring Harbor......Page 32
Cre-Lox......Page 33
NIH and the Memoranda of Understanding (MOU)......Page 34
NIH Policy......Page 35
Reach-Through Rights......Page 37
Sharing Mice within Academia......Page 39
Jackson Mouse Repository......Page 40
The Research Exemption......Page 41
References......Page 43
Introduction......Page 46
Setting the Stage......Page 47
The Researcher/Repository Interface......Page 48
Donor Benefits......Page 49
Finding and Obtaining Mice......Page 50
Mouse Mutant Resource (MMR)......Page 51
Mouse Mutant Regional Resource Centers (MMRRC)......Page 52
RIKEN Bioresource Center (BRC)......Page 53
References......Page 54
History of MGI......Page 58
Integrated Data within MGI......Page 61
Gene Expression Data......Page 62
Mouse Tumor Biology Data......Page 63
Alleles and Phenotype Data......Page 66
Summary......Page 71
References......Page 72
Establishment of the Resource Information Archive in Japan......Page 76
Riken GSC/BRC DB......Page 77
Future Directions......Page 78
Introduction: Representing Mutant Mouse Phenotypes......Page 80
Pathbase and the Development of a Mouse Pathology Ontology......Page 83
The Mouse Pathology (MPATH) Ontology......Page 85
Other Approaches to a Pathology Description Framework......Page 88
The Development of MPATH: Problems and Pitfalls in the Classification of Lesions......Page 90
Diseases and the Pathologic Responses......Page 91
Morphological and Molecular Descriptions for Pathology......Page 92
Handling Mutant Phenotypes......Page 94
References......Page 96
Biological Methods for Archiving and Maintaining Mutant Laboratory Mice......Page 102
Introduction......Page 103
Cryopreserving the Mouse......Page 104
Embryo Cryopreservation: An Overview......Page 105
Equipment and Reagents......Page 106
Freezing Procedure......Page 107
Thawing......Page 108
Freeze-Drying Method......Page 109
Rehydration of Freeze-Dried Spermatozoa and ICSI......Page 110
Equipment and Reagents......Page 111
Embryo Cooling......Page 112
Thawing......Page 113
Cryopreservation of Mouse Spermatozoa......Page 114
Solutions......Page 116
Method Used for In Vitro Fertilisation......Page 117
Sperm Sample Preparation-Freshly Harvested Sperm......Page 118
Sperm Sample Preparation-Cryopreserved Sperm......Page 119
Cryopreservation of Mouse Oocytes......Page 120
Freezing Procedure......Page 121
Thawing......Page 122
Solutions......Page 123
Thawing......Page 124
Long-Term Survival of Cryopreserved Germplasm......Page 125
Concluding Remarks......Page 126
References......Page 127
Appendix......Page 129
Introduction......Page 132
History of Somatic Cell Cloning and Application......Page 133
Technical Determinants in Cloning......Page 134
The Abnormality of Cloned Mice......Page 135
Generation of ntES Cell Lines from Adult Somatic Cells......Page 137
Acknowledgment......Page 140
References......Page 141
Introduction......Page 144
Stages When Abnormalities Develop......Page 145
Typical or Varied Abnormalities......Page 146
Effects of Donor Cells......Page 147
References......Page 148
Gene Trapping-Principle, Advantages, and Disadvantages......Page 150
Cre-Mutant Lox Site-Specific Integration System......Page 153
pU-17 Exchangeable Trap Vector......Page 158
References......Page 159
Introduction: Genetic Contaminations Reported in the Past......Page 162
Spontaneous Mutant and Genetically Engineered Mouse Phenotypes Vary with Genetic Background......Page 163
Markers for Genetic Monitoring......Page 165
Sets of Markers for Genetic Quality Testing......Page 166
Test Frequency......Page 168
Genetic Monitoring for Cell Lines, Gametes, and Embryos......Page 169
Strain Identification......Page 171
Genotyping of Transgenes and Targeted Genes......Page 172
Conclusion......Page 174
References......Page 175
Introduction......Page 176
Microbial Exclusion Planning......Page 177
Elements of Routine Microbiologic Monitoring......Page 179
References......Page 182
Effect of Intestinal Flora on Phenotype......Page 184
Colon Tumors in Gnotobiotic RasH2 Transgenic Mice......Page 185
Standardization of Intestinal Flora......Page 187
References......Page 189
Relation between H. pylori Infection and Stomach Cancer in Mongolian Gerbils Treated with Chemical Carcinogens......Page 192
Phenotypic Classification of Intestinal Metaplasia and Regulation of Gastric and Intestinal Epithelial Phenotypic Expression by Specific Transcription Factors......Page 193
Reversibility of Tumorlike Lesions Induced by Hp in Mongolian Gerbils......Page 194
Is IM a Premalignant Lesion in Gastric Cancer?......Page 195
Gastric and Intestinal Phenotypic Expression of Gastric Cancer Cells......Page 196
Conclusion......Page 197
References......Page 198
Professional Use of Mutant Laboratory Mice in Research......Page 204
Characterizing Mutant Mice......Page 205
Spontaneous Mutants......Page 207
Identifying Mutant Mice Resulting from Mutations in Genes of Interest......Page 208
Xenographs......Page 209
Exogenous Compounds......Page 210
Mouse Genome Informatics Web Site......Page 211
Searching MGI by Gene Name or Symbol......Page 212
Searching MGI by Phenotype Keywords......Page 215
Searching MGI by Sequence Similarity......Page 217
Obtaining Mice for Use in Research......Page 218
Nonprofit Institutions......Page 219
Commercial Vendors......Page 221
Other Web-Based Resources Relevant to Skin and Hair Research......Page 222
References......Page 223
Introduction......Page 230
Research Approaches to Mutant Mouse Characterization......Page 231
Colony Establishment......Page 233
Phenotypic Characterization, General Issues......Page 234
Which Mice and How Many to Analyze?......Page 235
Comparison with Human and Domestic Animal Diseases......Page 236
Summary......Page 237
References......Page 238
Common Diseases Found in Inbred Strains of Laboratory Mice......Page 242
References......Page 244
Introduction......Page 252
ApcMin Mice, ApcD716 Mice, Apc1638N Mice, and Other Apc Mutant Mice......Page 253
Modifier Genes of Apc Intestinal Polyposis......Page 255
Mutations in DNA Mismatch Repair Genes......Page 256
Mouse Models for Gastrointestinal Hamartoma Syndromes......Page 257
Mouse Models for Hereditary Nonpolyposis Colon Cancer......Page 259
Colon Cancer Models with Mutations in Other Genes......Page 260
Mouse Models for Tumor Chemotherapy and Chemoprevention......Page 262
References......Page 264
Note Added in proof......Page 270
Introduction......Page 272
Cyp11a1 Null Mice Rescued with Corticosteroids Exhibit Growth Retardation......Page 274
Sex Reversal and Cryptorchidism of Cyp11a1 Null Male Mice......Page 275
Defect of Male Accessory Sex Organ Differentiation in Cyp11a1 Null Mice......Page 276
Genital Tract Infantilism of Cyp11a1 Null Female Mice......Page 277
Histological Modifications in Genital Tract of Cyp11a1 Null Mice......Page 278
Discussion......Page 279
References......Page 280
External Genitalia Development: A Model System to Study Organogenesis......Page 282
External Genitalia Development: A Model for Organogenesis?......Page 284
Emergence of Growth Factors: Fibroblast Growth Factors (FGFs) as a Beginning of Growth Factor Analysis of External Genitalia Formation......Page 288
Role of Fgf10 During External Genitalia Formation: The First Case of Gene Knock-Out Mouse Model for External Genitalia Development......Page 289
Genes Necessary for Setting Initial Developmental Field: Genetic Cascades Necessary for External Genitalia Outgrowth Induction......Page 290
The Role of Developing Epithelia in Epithelial-Mesenchymal Interaction: The Development of External Genitalia and Embryonic Gut......Page 291
Role of Bone Morphogenetic Protein (Bmp) Genes in External Genitalia Development......Page 292
Acknowledgment......Page 293
References......Page 294
Introduction......Page 298
RA Receptors Have Pleiotropic and Mostly Redundant Developmental Functions......Page 300
Retinoic Acid Synthesis Is Enzymatically Regulated in Embryonic Tissues......Page 301
Differential Expression Patterns of Murine Retinaldehyde Dehydrogenases......Page 302
RALDH2 Is Mainly Responsible for RA Synthesis at Early Embryonic Stages......Page 304
RA-Rescue of Null Mutant Embryos Unveils Additional RALDH2 Developmental Functions......Page 305
Decreased RALDH2-Mediated RA Synthesis Leads to a DiGeorge Syndromelike Phenotype......Page 307
Conditional Mutagenesis: An Alternative Approach to Investigate Tissue-Specific RALDH2 Functions......Page 308
References......Page 310
Introduction......Page 314
Phenotypes of the Ror1 and Ror2 Mutant Mice......Page 316
Comparison of Phenotypes of Ror2 and Wnt5a Mutant Mice......Page 317
Physical and Functional Interactions Between Ror2 and Wnt5a......Page 318
Acknowledgments......Page 319
References......Page 320
c......Page 322
d......Page 323
f......Page 324
g......Page 325
i......Page 326
m......Page 327
n......Page 329
p......Page 330
r......Page 331
t......Page 332
x......Page 333