The book gives a broad overview of recombinant DNA techniques for the behavioral neuroscientist, with illustrative examples of applications. Species covered include rodents (mainly mice), Drosophila melanogaster, Caenorhabditis elegans and Danio rerio. Experimental techniques required to characterize the behavioral phenotypes of mutant animals is provided. Several aspects of novel molecular-genetic techniques are overviewed and possible research strategies are explained. The sections of the book start with general descriptions of techniques followed by illustrative examples.
It is divided into six sections. Section 1, bioinformatics and genomics research. Section 2, top-down strategies, where the researcher starts with the phenotype and then analyzes the associated genes; bottom-up strategies, where the physiological chain leading to a phenotype is analyzed starting from the gene product. Section 3, transgenic approaches in rodents including overexpressing foreign genes and gene-targeting; systemic manipulation approaches directly targeting the central nervous system and methods used with invertebrates. Section 4, methods used to evaluate relevant behavioral phenotypes, including learning and aggression. Section 5, examples on molecular brain research in man. Section 6, ethical aspects of research in this field.
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an online database of psychiatric genetics linkage, association, and genome mapping projects (N.M. Williams, I. Fenton, M.J. Owen). 1.4. Experimental design and statistical inference (D. Wahlsten). 2. Searching for New Genes. 2.1. Spontaneous and Induced Mutations with Effects on Neural and Behavioral Traits. 2.1.1. Mapping single locus mutations in mice: towards gene identification of neurological traits (W.N. Frankel, B.A. Taylor). 2.1.2. Experimental strategies for mapping quantitative trait loci (QTL) analysis in laboratory animals (D.A. Blizard, A. Darvasi). 2.1.3. Linkage strategies for mapping genes for complex traits in man (L. Almasy, J. Blangero). 2.1.4. Genetic association studies in behavioral neuroscience (P. Gorwood). 2.1.5. DNA pooling in allelic association studies (N.M. Williams, M.J. Owen). 2.1.6. Research strategies for the analysis of neurological mutants of the mouse (C. Sotelo, J. Mariani). 2.1.7. Genetic dissection of mouse behavior using induced mutagenesis (L.H. Pinto, J.S. Takahashi). 2.1.8. Mutagenesis in zebra fish: studying the brain dopamine systems (S. Guo, W. Driever, A. Rosenthal). 2.1.9. Behavioral and electrophysiological screens for isolating zebra fish mutants with visual system defects (J.E. Dowling). 2.2. Finding Genes with Phenotypical Effects on Neural and Behavioral Phenotypes on the Basis of Gene-Expression. 2.2.1. Subtractive cDNA hybridization and the brain: then, now and tomorrow (J.B. Watson). 2.2.2. Applying differential display to brain research (C.V. Mello, E.D. Jarvis). 2.2.3. Brain region-specific genes: the hippocampus (B.S. Pickard, B.J. Davies, K.A. Rose, G. Stapleton, M. Steel, R. Lathe). 2.2.4. Application of real-time RT-PCR for quantification of gene expression (J. Winer, N. Shinsky, R. Gerlai, P.M. Williams). 2.2.5. Analyzing genomic DNA discordance between monozygotic twins (J. Bouchard, C. Foulon, N. Storm, G.H. Nguyen, C.L. Smith). 3. Manipulating Known Genes. 3.1. Transgenic Approaches in Rodents. 3.1.1. Embryonic stem cells and gene targeting (A. Wynshaw-Boris, L. Garrett, A. Chen, C. Barlow). 3.1.2. Generation of transgenic mice by pronuclear DNA injection (A. Wynshaw-Boris, L. Garrett, A. Chen, C. Barlow). 3.1.3. Brain region-specific and temporally restricted gene knockout using the Cre recombinase system (J.Z. Tsien). 3.1.4. Regulated temporal and spatial expression of mutants of CaMKII and calcineurin with the tetracycline-controlled transactivator (tTA) and reverse tTA (rtTA) systems (I.M. Mansuy, M. Mayford, E.R. Kandel). 3.1.5. The use of targeted point mutants in the study of learning and memory (K.P. Giese). 3.1.6. Genetic dissection of a postsynaptic multiprotein complex controlling synaptic plasticity and learning in the mouse (S.G.N. Grant). 3.1.7. Molecular genetic analysis of glutamate receptor function in long-term potentiation in the mouse hippocampus (Z. Jia, Y.M. Lu, N. Agopyan, J. Roder). 3.1.8. Targeting aggression in mice (R.J. Nelson, L.J. Kriegsfeld). 3.1.9. Behavioral analysis of Dvl1-deficient mice reveals a role for the Dvl1 gene in social behaviors and sensorimotor gating (R. Paylor, N. Lijam, M.P. McDonald, J.N. Crawley, D.J. Sussman, A. Wynshaw-Boris). 3.1.10. Targeting genes associated with mammalian behavior: past mistakes and future solutions (R. Gerlai). 3.2. Systemic Manipulation. 3.2.1. Gene transfer and therapy in the CNS (M.-C. Senut, S.T. Suhr, F.H. Gage). 3.2.2. Adenovirus vectors for gene transfer into the central nervous system (M. Barkats, O. Corti, J. Mallet). 3.2.3. Regulatable adenoviral technology in behavioural neuroscience (J.B. Uney, B. Geddes, E.C. Warburton, T. Harding). 3.2.4. Antisense oligonucleotides to selectively suppress gene expression in the brain (G. Pollio, A. Maggi). 3.2.5. Application of recombinant proteins, peptides and antibodies in exploring the role of Src in regulating synaptic function (M.W. Salter). 3.2.6. The use of immunoadhesins in neurobiology (D.L. Shelton). 3.2.7. Protein targeting in the functional analysis of EphA receptors: the use of immunoadhesins (R. Gerlai, N. Shinsky, A. Shih, P. Williams, J. Winer, M. Armanini, P. Moran, B. Cairns, J. Winslow, W.-Q. Gao, H.S. Phillips). 3.3. Invertebrates. 3.3.1. A novel approach to Drosophila neurophysiology: the targeted expression of aequorin (P. Rosay, K. Kaiser, J.D. Armstrong). 3.3.2. Behavior-genetic and molecular analysis of naturally occurring variation in Drosophila larval foraging behavior (M.B. Sokolowski, C.A.L. Riedl). 3.3.3. Structure-function analysis of the Drosophila optic lobes (G. Pflugfelder). 3.3.4. Testing associative learning in Drosophila (T. Préat). 3.3.5. Caenorhabditis elegans and the genetics of learning (K.R. Peters, J.A. Galloway, C.H. Rankin). 3.3.6. Forward genetic approaches in the analysis of Caenorhabditis elegans (A.C. Hart). 3.3.7. Analyzing neuropeptide function in Caenorhabditis elegans by reverse genetics (C. Li). 4. Evaluating Behavioral Phenotypes in Rodents. 4.1. Ethological approaches in behavioral neurogenetic research (R. Gerlai). 4.2. What animals remember about past events: an ethological approach (N.S. Clayton). 4.3. Motor performance of spontaneous murine mutations with cerebellar atrophy (R. Lalonde, C. Strazielle). 4.4. Methodological considerations for testing learning in mice (W.E. Crusio). 4.5. Drug and alcohol dependence-related behaviors (J.C. Crabbe, C.L. Cunningham). 4.6. Evaluating anxiety in rodents (J.N. Crawley). 4.7. A neurobehavioral system approach in rats to study the molecular biology of fear (J.B. Rosen, S. Malkani, K. Wallace, B. Thompson). 4.8. Measuring aggression in the mouse (P.L. Roubertoux, I. Le Roy, S. Mortaud, F. Perez-Diaz, S. Tordjman). 4.9. Methodological issues in the assessment of behavioral development in laboratory mice (P.E. Wainwright). 4.10. Understanding maternal behavior: analyses of behavior, c-Fos expression and calmodulin binding proteins in the medial preoptic area and other areas of the rat brain (A.S. Fleming, D.H. O'Day). 4.11. Measuring rodent exploratory behavior (C. Belzung). 5. Human Neurobehavioral Disorders: from Molecular Genetics to Genetic Animal Modes. 5.1. Psychiatric genetics
a current perspective (D.F. Levinson). 5.2. Defining phenotypes for psychiatric genetics (M. Nosten-Bertrand, F. Bellivier, M. Leboyer). 5.3. Trinucleotide repeat disorders (G. Sandberg, K. Lindblad, B.A. Oostra, M. Schalling). 5.4. Finding liability genes for schizophrenia (N.J.O. Jacobsen, N.M. Williams, M.J. Owen). 5.5. Genetics of idiopathic epilepsy (L. Bate, M. Gardiner). 5.6. Identification and functional analysis of genes and genetic risk factors in Alzheimer's disease (C. De Jonghe, C. Van Broeckhoven). 5.7. Aging, Alzheimer's disease and frameshift mutations (W.H. Van den Hurk, F.W. Van Leeuwen, G.J.M. Martens). 5.8. Transgenic mouse models of Alzheimer's disease (K. Duff). 5.9. Modelling Down syndrome in mice (M. Dierssen, M. Pritchard, C. Fillat, M. Arbonés, J.M. Aran, J. Flórez, X. Estivill). 6. Ethical Considerations. 6.1. Genes and human behavior: scientific and ethical implications of the human genome project (J. Beckwith). 6.2. Ethical issues and psychiatric genetics (A.E. Farmer, P. McGuffin). 6.3. Ethical implications of knock-out and transgenesis techniques for animal research (L.M. Houdebine). Subject index.
Dr. Wim Crusio is a Research Director with the French National Centre for Scientific Research (Centre National de la Recherche Scientifique, CNRS) and adjunct director of the Institut de Neurosciences Cognitives et Intégratives d'Aquitaine at the University of Bordeaux. Prior to this, he held positions as Professor of Psychiatry in the Brudnick Neuropsychiatric Research Institute at the University of Massachusetts Medical School and as senior researcher at the Universities of Heidelberg (Germany) and Paris V (France). He was one of the founders of the International Behavioural and Neural Genetics Society (IBANGS), founding editor-in-chief of Genes, Brain and Behavior (G2B), and associate editor or member of the editorial board of over a dozen scientific journals, including The Behavioral and Brain Sciences. He regularly serves as reviewer, both for scientific journals and for granting agencies, including the NIH, NSERC, European Union, and others. He is a recipient of the IBANGS Distinguished Service Award.