Gaultier Genetic Basis for Respiratory Control Disorders

1. Auflage 2007
ISBN: 978-0-387-70765-5
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 324 Seiten

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