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Establishing Genotype/Phenotype Relationships: Gene Targeting as an Experimental Approach

Published online by Cambridge University Press:  01 April 2022

Sylvia Culp
Sylvia Culp*
Affiliation:
Western Michigan University
*
†Department of Philosophy, Western Michigan University, Kalamazoo, MI 49008 or to sylvia.culp@wmich.edu.
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Abstract

In this paper, I examine an experimental technique, gene targeting, used for establishing genotype/phenotype relationships. Through analyzing a case study, I identify many pitfalls that may lead to false conclusions about these relationships. I argue that some of these pitfalls may seriously affect gene targeting's usefulness for associating phenotypes with genes cataloged by the Human Genome Project. This case also shows the use of gene targeted mice as model systems for studying genotype/phenotype relationships in humans. Moreover, I argue that it reveals the weakness of one attempt to draw conclusions about the biological determination of sexual and aggressive behaviors in humans.

Type
Symposium: Complexity and Experimentation in Molecular Biology
Information
Philosophy of Science , Volume 64 , Issue S4: Supplement. Proceedings of the 1996 Biennial Meetings of the Philosophy of Science Association. Part II: Symposia Papers Dec., 1997 , 1997 , pp. S268 - S278
Copyright
Copyright © Philosophy of Science Association 1997

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Footnotes

‡

In preparing this paper I have benefited from the comments of Arthur Falk and three anonymous referees for this journal.

References

Bechtel, W. and Richardson, R. C. (1993), Discovering Complexity: Decomposition and Localization as Strategies in Scientific Research. Princeton: Princeton University Press.Google Scholar
Brunner, H. G., Nelen, M., Breakefield, X. O., Ropers, H. H., and van Oost, B. A. (1993), “Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A”, Science 262: 578–580.10.1126/science.8211186CrossRefGoogle ScholarPubMed
Chien, K. R. (1996), “Genes and Physiology: Molecular Physiology in Genetically Engineered Animals”, Journal of Clinical Investigation 97: 901–909.10.1172/JCI118512CrossRefGoogle ScholarPubMed
Clark, A. F., Sharp, M. G. F., and Mullins, J. J. (1996), “Gene Targeting and its Application to Basic Hypertension Research”, Clinical Science 90: 435–446.CrossRefGoogle ScholarPubMed
Crawley, J. N. (1996), “Unusual Behavioral Phenotypes of Inbred Mouse Strains”, Trends in Neurosciences 19: 181–182.10.1016/S0166-2236(96)20021-9CrossRefGoogle ScholarPubMed
Crusio, W. E. (1996), “Gene-targeting Studies: New Methods, Old Problems”, Trends in Neurosciences 19: 186–187.CrossRefGoogle ScholarPubMed
Culotta, E. and Koshland, D. E. Jr. (1992), “NO News Is Good News”, Science 258: 1862–1865.CrossRefGoogle ScholarPubMed
Dawson, T. M. and Dawson, V. L. (1996), “Nitric Oxide Synthase: Role as a Transmitter/Mediator in the Brain and Endocrine System”, Annual Review of Medicine 47:219–227.Google ScholarPubMed
Gerlai, R. (1996a), “Gene-targeting Studies of Mammalian Behavior: Is It the Mutation or the Background Genotype?” Trends in Neurosciences 19: 177–181.CrossRefGoogle Scholar
Gerlai, R. (1996b), “Gene Targeting in Neuroscience: the Systemic Approach”, Trends in Neurosciences 19: 188–189.Google Scholar
Huang, P. L., Dawson, T. M., Bredt, D. S., Snyder, S. H., and Fishman, M. C. (1993), “Targeted Disruption of the Neuronal Nitric Oxide Synthase Gene”, Cell 75: 1273–1286.10.1016/0092-8674(93)90615-WCrossRefGoogle ScholarPubMed
Huang, Z., Huang, P. L., Panahian, N., Dalkara, T., Fishman, M. C., and Moskowitz, M. A. (1994), “Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase”, Science 265: 1883–1885.CrossRefGoogle ScholarPubMed
Koller, B. H. and Smithies, O. (1992), “Altering Genes in Animals by Gene Targeting”, Annual Review of Immunology 10: 705–730.10.1146/annurev.iy.10.040192.003421CrossRefGoogle ScholarPubMed
Koshland, D. E. Jr. (1989), “Sequences and Consequences of the Human Genome”, Science 246: 189.10.1126/science.2799380CrossRefGoogle ScholarPubMed
Koshland, D. E. Jr. (1992), “The Molecule of the Year”, Science 258: 1861.10.1126/science.1470903CrossRefGoogle Scholar
Lander, E. S. (1996), “The New Genomics: Global Views of Biology”, Science 274: 536–539.10.1126/science.274.5287.536CrossRefGoogle ScholarPubMed
Nelson, R. J., Demas, G. E., Huang, P. L., Fishman, M. C., Dawson, V. L., Dawson, T. M., and Snyder, S. H. (1995), “Behavioural Abnormalities in Male Mice Lacking Neuronal Nitric Oxide Synthase”, Nature 378: 383–386.CrossRefGoogle ScholarPubMed
O'Dell, T. J., Huang, P. L., Dawson, T. M., Dinerman, J. L., Snyder, S. H., Kandel, E. R., and Fishman, M. C. (1994), “Endothelial Nos and the Blockade of LTP by Nos Inhibitors in Mice Lacking Neuronal Nos”, Science 265: 542–546.CrossRefGoogle ScholarPubMed
Rubin, E. M. and Barsh, G. S. (1996), “Biological Insights Through Genomics: Mouse to Man”, Journal of Clinical Investigation 97: 275–280.10.1172/JCI118413CrossRefGoogle ScholarPubMed
Waters, C. K. (1994), “Genes Made Molecular”, Philosophy of Science 61:163–185.10.1086/289794CrossRefGoogle Scholar
Weissenbach, J. (1996), “Landing on the Genome”, Science 274: 479.CrossRefGoogle ScholarPubMed