Mouse models of developmental genetic disease

Approximately three percent of newborn humans have congenital anomalies with significant cosmetic and/or functional consequences. Much of our ability to understand what has gone awry in these birth defects rests with development of animal models for them; the mouse has emerged as the model organism of choice for these studies. This volume reviews mouse models of specific developmental genetic diseases, including neural tube defects; cleft lip and/or palate; congenital heart disease; ciliopathies; hereditary deafness and others to provide conceptual insight into congenital anomalies generally. The interplay between clinical observation and murine model systems is expected to yield deep insight into mammalian developmental processes and the emergence of effective preventive and/or therapeutic strategies.

Irene E. Zohn and Anjali A. SarkarAmel Gritli-LindeKaren A. Schachter and Robert S. KraussAnne MoonRobyn J. Quinlan and Jonathan L. Tobin and Philip L. BealesPatricia D. WilsonTatiana V. Cohen and Colin L. StewartMichel Leibovici and Saaid Safieddine and Christine PetitGlen B. Banks and Jeffrey S. Chamberlain

Contributors	p. ix
Preface	p. xi
1 Modeling Neural Tube Defects in the Mouse	p. 1
1 Introduction	p. 2
2 Examples of Mouse as a Multifactorial Threshold Model for the Inheritance of NTDs	p. 6
3 Mouse Models of NTDs Have Identified Candidate Genes for NTDs in Humans	p. 11
4 Mouse as a Model for the Elucidation of the Molecular Mechanisms of Gene-Environment Interactions Contributing to NTDs	p. 21
5 Mouse as a Model for Developing Approaches to Prevent NTDs	p. 23
6 Conclusions and Future Directions	p. 26
References	p. 26
2 The Etiopathogenesis of Cleft Lip and Cleft Palate: Usefulness and Caveats of Mouse Models	p. 37
1 Introduction	p. 38
2 The Genetic Etiology of CL/P and CPO	p. 41
3 Embryonic Development of the Upper Lip, Primary Palate and Secondary Palate	p. 53
4 Cellular and Molecular Mechanisms Governing Lip and Palate Development: Insights from Mouse Models for CL/P and CPO	p. 56
5 Caveats for Using Mouse Models for Orofacial Clefting	p. 114
6 Concluding Remarks	p. 119
Acknowledgements	p. 120
References	p. 120
3 Murine Models of Holoprosencephaly	p. 139
1 Introduction	p. 140
2 Human HPE	p. 141
3 Development of the Forebrain-A Delicate Balance	p. 145
4 Mouse Models of HPE	p. 147
5 Conclusions and Perspectives	p. 160
Acknowledgments	p. 162
References	p. 162
4 Mouse Models of Congenital Cardiovascular Disease	p. 171
1 Introduction	p. 172
2 An Overview of Cardiac Development in the Mouse	p. 173
3 From Human to Mouse: Using Mouse Models to Understand How Mutations Identified in Humans Cause Congenital Cardiovascular Disease	p. 189
4 From Mouse to Human: Using Mouse Models to Discover Novel Factors and Pathways That Regulate Cardiovascular Development	p. 209
5 Conclusion	p. 225
Acknowledgments	p. 226
References	p. 227
5 Modeling Ciliopathies: Primary Cilia in Development and Disease	p. 249
1 The Human Ciliopathies	p. 250
2 Bardet-Biedl Syndrome	p. 251
3 Alstrom Syndrome	p. 263
4 Polycystic Kidney Disease	p. 264
5 Nephronophthisis	p. 265
6 Meckel Syndrome	p. 267
7 Joubert Syndrome	p. 268
8 Jeune Syndrome	p. 269
9 Oral-Facial-Digital Syndrome	p. 269
10 The Structure and Function of the Cilium	p. 270
11 Cilia and Development	p. 276
12 Therapies for Cystic Disease	p. 287
13 Concluding Remarks	p. 289
References	p. 292
6 Mouse Models of Polycystic Kidney Disease	p. 311
1 Introduction	p. 312
2 The PKD Genes	p. 313
3 Genocopy Mouse Models of PKD	p. 314
4 PKD: The Human Diseases	p. 318
5 Phenotypic Mouse Models of PKD	p. 321
6 Normal Mammalian Kidney Development	p. 324
7 The PKD Proteins	p. 326
8 Mechanisms of Renal Cyst Formation	p. 332
9 Future Perspectives	p. 339
Acknowledgments	p. 340
References	p. 340
7 Fraying at the Edge: Mouse Models of Diseases Resulting from Defects at the Nuclear Periphery	p. 351
1 Introduction	p. 352
2 The Laminopathies	p. 353
3 Mouse Models for the A-Type Laminopathies	p. 354
4 Progeroid Syndromes	p. 361
5 Laminopathies Associated with Mutations in the B-Type Lamins	p. 365
6 Molecular Mechanisms Underlying the Laminopathies	p. 366
7 Disease and Anomalies Caused by Mutations in Other NE Associated Proteins	p. 371
8 Conclusions	p. 376
References	p. 377
8 Mouse Models of Human Hereditary Deafness	p. 385
1 Introduction	p. 386
2 The Mammalian Peripheral Auditory System	p. 387
3 Human Congenital Deafness	p. 401
4 Mouse Models for Human Hereditary Deafness	p. 404
5 Concluding Remarks	p. 419
Acknowledgments	p. 419
References	p. 420
9 The Value of Mammalian Models for Duchenne Muscular Dystrophy in Developing Therapeutic Strategies	p. 431
1 Introduction	p. 432
2 The mdx Mouse Models of DMD	p. 435
3 mdx:utrophin Double Knockout Mouse Model	p. 440
4 The cxmd Canine Model	p. 442
5 Conclusions	p. 443
Acknowledgments	p. 444
References	p. 444
Index	p. 455
Contents of Previous Volumes	p. 467

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