Genetic Models of Schizophrenia

Copyright......Page 1
List of Contributors......Page 2
Key features......Page 3
Advantage of genetic animal models......Page 4
Possible limitations of genetic animal models......Page 5
References......Page 6
Introduction......Page 8
Region-specific targeting by in utero gene transfer......Page 10
Summary......Page 11
Conditional targeting system......Page 12
References......Page 13
Introduction......Page 15
Inducible expression of the fragment of human DISC1......Page 16
Spatial aspects of SZ etiology and/or pathophysiology......Page 18
Stereotaxic viral injection: actual procedure......Page 19
Virus vectors for gene manipulation and their properties......Page 20
References......Page 22
References......Page 112
ENU-induced mutant mice for a next-generation gene-targeting system......Page 26
High-throughput mutation discovery systems......Page 27
Rates and spectrum of ENU-induced mutations......Page 28
Srr gene......Page 29
Acknowledgments......Page 30
Introduction......Page 32
Inducible gene expression models......Page 33
The tetracycline transactivator system......Page 34
Sdy/DBA and sdy/BL6 mice......Page 35
Inducible expression of the G-protein subunit gas......Page 38
PDE4 mice......Page 39
Zebrafish as a model to study brain development......Page 40
References......Page 41
NR1 knockdown mice as a representative model of the glutamate hypothesis of schizophrenia......Page 45
Comparing genetic and pharmacological models of NMDA receptor hypofunction......Page 46
Cortical dopaminergic hypofunction......Page 48
NR1-KD as a representative model of NMDA receptor hypofunction......Page 49
References......Page 50
Dopaminergic hyperfunction in the striatum......Page 53
Modeling increased density of D2 receptors in the striatum of the mouse......Page 55
References......Page 58
PDE1 mice......Page 60
Behavior......Page 83
References......Page 64
Introduction......Page 67
Seven DISC1 mouse models......Page 68
Cellular and histological abnormalities in DISC1 mouse models......Page 71
Neurite outgrowth in primary cultures from DISC1 mouse models......Page 72
Concluding remarks......Page 74
References......Page 76
Dysbindin-1 in schizophrenia......Page 79
The Dtnbp1sdy mutation......Page 80
Biogenesis of lysosome-related organelles complex 1 (BLOC-1) proteins......Page 81
Synaptic transmission......Page 82
References......Page 85
Introduction......Page 87
Molecular genetic techniques in zebrafish......Page 88
Supporting Information......Page 91
Zebrafish as a model to determine susceptibility gene function......Page 92
References......Page 93
Introduction......Page 97
Genetics in flies......Page 98
DISC1 analyses in flies......Page 99
Perspectives......Page 101
References......Page 103
Schizophrenia as an affliction of the association cortices......Page 106
The greatly increased complexity of primate PFC neurons......Page 107
Pyramidal cell network connections as a key site of vulnerability in schizophrenia......Page 108
The utility of AAV vectors in modeling schizophrenia susceptibility......Page 110
Relevance to DISC1 function......Page 111
D......Page 115
I......Page 116
Q......Page 117
Z......Page 118