Gaultier Genetic Basis for Respiratory Control Disorders

1. Auflage 2007
ISBN: 978-0-387-70765-5
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 324 Seiten

Bringing together top-level contributions on all aspects of the subject, this book provides an overview of the recent advances in the genetics of respiratory control in health and disease. It also shows how combined studies in humans and mouse models have helped to improve our understanding of the mechanisms that underlie genetically determined respiratory control disorders with the goal of developing new therapeutic interventions.

Autoren/Hrsg.

Gaultier, Claude

Inhaltsverzeichnis

1;Introduction;6
2;Preface;7
3;Contributors;9
4;Contents;16
5;Abbreviations;21
6;1. Respiratory control disorders: from genes to patients and back;28
6.1;1.1 Introduction;28
6.2;1.2 Effect of sleep on breathing;29
6.3;1.3 Diagnostic approaches to the patient with suspected abnormalities in respiratory control;30
6.4;1.4 Potential consequences of delayed diagnosis and treatment;31
6.5;1.5 Where do we go from here?;31
6.6;1.6 Conclusion;32
6.7;Acknowledgements;32
6.8;References;33
7;2. Hereditary aspects of respiratory control in health and disease in humans;36
7.1;2.1 Introduction;36
7.2;2.2 Inter-individual variation in human ventilatory control;36
7.3;2.3 Population and species differences;38
7.4;2.4 Familial clusters;39
7.5;2.5 Genetics vs. environment;43
7.6;2.6 Locus of hereditary effects;43
7.7;2.7 Conclusion;47
7.8;References;47
8;3. Phox2b and the homeostatic brain;51
8.1;3.1 Introduction;51
8.2;3.2 Expression pattern of Phox2 genes;51
8.3;3.3 Gross phenotype of mouse mutants for Phox2 genes;56
8.4;3.4 Cellular functions of Phox2 genes;59
8.5;3.5 Ancestry of the homeostatic brain;64
8.6;Conclusion;64
8.7;References;64
9;4. Congenital central hypoventilation syndrome: from patients to gene discovery;71
9.1;4.1 Introduction;71
9.2;4.2 Clinical presentation of CCHS;72
9.3;4.3 Genetic mutations in CCHS;76
9.4;4.4 Phenotype-genotype correlations;77
9.5;4.5 Conclusion;78
9.6;References;78
10;5. Structural and functional brain abnormalities in Congenital Central Hypoventilation Syndrome;82
10.1;5.1 Introduction;82
10.2;5.2 Structural injury and functional deficits in CCHS;83
10.3;5.3 Imaging findings;84
10.4;5.4 Cardiovascular control deficits;89
10.5;5.5 Potential mechanisms in injury;90
10.6;5.6 Conclusion;91
10.7;Acknowledgements;92
10.8;References;92
11;6. In vitro studies of PHOX2B gene mutations in congenital central hypoventilation syndrome;96
11.1;6.1 Introduction;96
11.2;6.2 PHOX2B polyalanine expansions;98
11.3;6.3 PHOX2B frameshift mutations;102
11.4;6.4 Conclusion;104
11.5;References;106
12;7. Sudden infant death syndrome: study of genes pertinent to cardiorespiratory and autonomic regulation;109
12.1;7.1 Introduction;109
12.2;7.2 Cardiac channelopathy genes in SIDS;110
12.3;7.3 Serotonergic system genes in SIDS;112
12.4;7.4 Autonomic Nervous System (ANS) genes in SIDS;115
12.5;7.5 Nicotine metabolizing genes in SIDS;119
12.6;7.6 Clinical significance;121
12.7;7.7 Conclusion and directions for future research on genetic factors in SIDS;125
12.8;References;125
13;8. The genetic basis for obstructive sleep apnea: what role for variation in respiratory control?;134
13.1;8.1 Introduction;134
13.2;8.2 OSA: Definition and health impact;134
13.3;8.3 OSA: Evidence for a familial basis;136
13.4;8.4 Genetic etiology-risk factors and their use as intermediate phenotypes;138
13.5;8.5 Ventilatory control as an intermediate OSA risk factor;139
13.6;8.6 Evidence for genetically determined ventilatory control abnormalities in familial OSA;145
13.7;8.7 Candidate genes for OSA that may operate through ventilatory control;146
13.8;8.8 Inferences from other conditions which involve ventilatory control deficits;148
13.9;8.9 Studies from animals;149
13.10;8.10 Pleiotropy;149
13.11;8.11 Conclusion;149
13.12;Acknowledgements;150
13.13;References;150
14;9. Apnea and irregular breathing in animal models: a physiogenomic approach;159
14.1;9.1 Introduction;159
14.2;9.2 Measuring ventilatory behavior;160
14.3;9.3 Defining apnea and ventilatory irregularity;162
14.4;9.4 Models of apnea;167
14.5;9.5 Model of recurrent apneas;168
14.6;9.6 Conclusion;170
14.7;References;170
15;10. Genetic determinants of respiratory phenotypes in mice;174
15.1;10.1 Introduction;174
15.2;10.2 Experimental methods and design;177
15.3;10.3 Observations and results;179
15.4;10.4 Significance of genetic determinants;184
15.5;10.5 Conclusion;185
15.6;References;186
16;11. Genes and development of respiratory rhythm generation;190
16.1;11.1 Introduction;190
16.2;11.2 Primordial embryonic rhythm in the neural tube;192
16.3;11.3 Parafacial rhythm generators : induction requires Krox20 in r3 and Hoxa1 in r4;194
16.4;11.4 Onset of the respiratory rhythm generation;196
16.5;11.5 Neurotrophic control of breathing;199
16.6;11.6 Brainstem modulatory controls of breathing;201
16.7;11.7 Conclusion;202
16.8;Acknowledgements;203
16.9;References;203
17;12. Transcription factor control of central respiratory neuron development;211
17.1;12.1 Introduction;211
17.2;12.2 Brainstem populations of neurons participating in central breathing control;212
17.3;12.3 Mouse mutants of transcription factors governing development of respiratory neurons and breathing control;215
17.4;12.4. Conclusion;232
17.5;References;233
18;13. Lessons from mutant newborn mice with respiratory control deficits;242
18.1;13.1 Introduction;242
18.2;13.2 Developmental respiratory control disorders;243
18.3;13.3 The newborn mouse;244
18.4;13.4 Mutant newborn mice as models of abnormal respiratory rhythm;245
18.5;13.5 Mutant newborn mice with abnormal chemosensitivity;248
18.6;13.6 Clinical relevance of mutant newborn mice models;252
18.7;13.7 Conclusion;253
18.8;References;254
19;14. Tentative mouse model for the congenital central hypoventilation syndrome: heterozygous phox2b mutant newborn mice;261
19.1;14.1 Introduction;261
19.2;14.2 Neonatal phenotype determination;262
19.3;14.3 Non-invasive ventilatory phenotyping in newborn mice;262
19.4;14.4 Sleep-disordered breathing in Phox2b+/- newborn mice;264
19.5;14.5 Sensitivity to CO;264
19.6;14.6 Sensitivity to hypoxia;266
19.7;14.7 Arousal response to hypoxia;267
19.8;14.8 Sensitivity to hyperoxia;268
19.9;14.9 Effects of ambient temperature;268
19.10;14.10 Cognitive evaluation of Phox2b;269
19.11;mutant mice;269
19.12;14.11 Comparison between Phox2b;269
19.13;and CCHS;269
19.14;phenotypes;269
19.15;14.12 Conclusion;271
19.16;References;272
20;15. Respiratory control abnormalities in necdin-null mice: implications for the pathogenesis of Prader- Willi syndrome;276
20.1;15.1 Introduction;276
20.2;15.2 Transgenic mouse models;276
20.3;15.3 Central Respiratory Deficit;277
20.4;15.4 General anatomical abnormalities within the CNS;281
20.5;15.5 Respiratory dysfunction in PWS;282
20.6;15.6 Conclusion;283
20.7;References;284
21;16. Possible role of bioaminergic systems in the respiratory disorders of Rett syndrome;287
21.1;16.1 Introduction;287
21.2;16.2 Clinical manifestations of respiratory disorders in RTT;288
21.3;16.3 Mouse models of RTT;289
21.4;16.4 Respiratory studies in mouse models of RTT;291
21.5;16.5 Bioaminergic systems, RTT and Mecp2-/;294
21.6;mice;294
21.7;16.6 Possible link between bioaminergic and respiratory alterations in mice and RTT patients;296
21.8;16.7 Conclusions: bioamines, respiration and RTT;298
21.9;Acknowledgements;299
21.10;References;299
22;17. Respiratory plasticity following intermittent hypoxia: a guide for novel therapeutic approaches to ventilatory control disorders?;306
22.1;17.1 Introduction;306
22.2;17.2 Deficiencies in respiratory motor neuron activity underlie some ventilatory control disorders;307
22.3;17.3 Intermittent hypoxia induced respiratory plasticity and metaplasticity;309
22.4;17.4 Compensatory plasticity during ventilatory control disorders;313
22.5;17.5 Possible therapeutic approaches for ventilatory control disorders: lessons from LTF?;316
22.6;17.6 Conclusion;320
22.7;Acknowledgements;320
22.8;References;321
23;Index;327