Behavior and mutagenesis screens: The importance of baseline analysis of inbred strains
Abstract
Random mutagenesis as a means of identifying the function of genes has been used extensively in a variety of model organisms. Until recently it has been used primarily in the identification of single-gene traits that cause visible and developmental mutations. However, this genetic approach also has the power to identify genes that control complex biological systems such as behavior. Mutagenesis screens for behavioral mutations require careful consideration of many factors, including choice of both assays and background strains for use in mutagenesis and subsequent mapping of the affected gene or genes. This paper describes behavioral assays for monitoring motor coordination on the accelerating rotarod, anxiety-related behaviors in the elevated zero maze and sensorimotor reactivity, gating, and habituation of acoustic startle. These five physiological or neurological behaviors can represent potential endophenotypes for a variety of neurological and psychiatric disorders. The significant degree of strain- and sex-specific differences in the performance of four inbred strains of mice (C57BL/6J, C3HeB/FeJ, DBA/2J, and 129/SvlmJ) in these behavioral assays illustrates the importance of performing baseline analysis prior to behavioral mutagenesis screens and genetic mapping of selected mutations.
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Parental lines of the 129SvJ-C57BL/6J F1 hybrid mice show differences in motor function, anxiety-related behavior, and sensorimotor responsivity, which may contribute to differential effects of partial nAChR agonists on depression-like behavior.
“previous research showed that the parental lines of the 129SvJ-C57BL/6J F1 hybrid mice show differences in motor function, anxiety-related behavior, and sensorimotor responsivity, which may contribute to the differential effects of partial nAChR agonists on depression-like behavior (Tarantino, Gould, Druhan, & Bucan, 2000).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Tarantino et al., 2000
Cites
Kessler, R. C. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950010008002 · Cited by 12,370 · see citing works
Genetics of Mouse Behavior: Interactions with Laboratory Environment
Crabbe, J. C., Wahlsten, D., & Dudek, B. C. (1999) · Science · doi:10.1126/science.284.5420.1670 · Cited by 1,666 · see citing works
Mutagenesis and Mapping of a Mouse Gene, <i>Clock</i> , Essential for Circadian Behavior
Vitaterna, M. H., King, D. P., Chang, A.-M., Kornhauser, J. M., Lowrey, P. L., McDonald, J. D., Dove, W. F., Pinto, L. H., Turek, F. W., & Takahashi, J. S. (1994) · Science · doi:10.1126/science.8171325 · Cited by 1,632 · see citing works
Positional Cloning of the Mouse Circadian Gene
King, D. P., Zhao, Y., Sangoram, A. M., Wilsbacher, L. D., Tanaka, M., Antoch, M. P., Steeves, T. D. L., Vitaterna, M. H., Kornhauser, J. M., Lowrey, P. L., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80245-7 · Cited by 1,382 · see citing works
Crawley, J. N., Belknap, J. K., Collins, A. C., Crabbe, J. C., Frankel, W. N., Henderson, N. D., HITZEMANN, R. J., Maxson, S. C., Miner, L. L., Silva, A. J., et al. (1997) · Psychopharmacology · doi:10.1007/s002130050327 · Cited by 1,372 · see citing works
A review of the validity and variability of the Elevated Plus-Maze as an animal model of anxiety
Hogg, S. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02126-4 · Cited by 1,169 · see citing works
Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype?
Gerlai, R. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)20020-7 · Cited by 881 · see citing works
Rogers, D. C., Fisher, E. M. C., Brown, S. D. M., Peters, J., Hunter, A. J., & Martin, J. E. (1997) · Mammalian Genome · doi:10.1007/s003359900551 · Cited by 795 · see citing works
Shepherd, J. K., Grewal, S. S., Fletcher, A., Bill, D. J., & Dourish, C. T. (1994) · Psychopharmacology · doi:10.1007/bf02244871 · Cited by 739 · see citing works
Elevated anxiety and antidepressant-like responses in serotonin 5-HT 1A receptor mutant mice
Heisler, L. K., Chu, H.-M., Brennan, T. J., Danao, J. A., Bajwa, P., Parsons, L. H., & Tecott, L. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15049 · Cited by 704 · see citing works
Hall, J. C. (1994) · Science · doi:10.1126/science.8209251 · Cited by 668 · see citing works
Conditioned Behavior in Drosophila melanogaster
Quinn, W. G., Harris, W. A., & Benzer, S. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.3.708 · Cited by 659 · see citing works
The quantitative measurement of motor inco-ordination in naive mice using an accelerating rotarod
Jones, B. J., & Roberts, D. J. (1968) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1968.tb09743.x · Cited by 583 · see citing works
Crawley, J. N., & Paylor, R. E. (1997) · Hormones and Behavior · doi:10.1006/hbeh.1997.1382 · Cited by 551 · see citing works
Experimental strategies for the genetic dissection of complex traits in animal models
Darvasi, A. (1998) · Nature Genetics · doi:10.1038/ng0198-19 · Cited by 540 · see citing works
Mice Lacking Dopamine D4 Receptors Are Supersensitive to Ethanol, Cocaine, and Methamphetamine
Rubinstein, M., Phillips, T. J., Bunzow, J. R., Falzone, T. L., Dziewczapolski, G., Zhang, G., Fang, Y., Larson, J. L., McDougall, J. A., Chester, J. A., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80365-7 · Cited by 473 · see citing works
Differences in fear motivated behaviors among inbred mouse strains
Trullás, R., & Skolnick, P. (1993) · Psychopharmacology · doi:10.1007/bf02244948 · Cited by 451 · see citing works
A Simple Genetic Basis for a Complex Psychological Trait in Laboratory Mice
Jonathan Flint, C., Corley, R. P., DeFries, J. C., Fulker, D. W., Gray, J. A., Miller, S., & Collins, A. C. (1995) · Science · doi:10.1126/science.7660127 · Cited by 438 · see citing works
Startle Habituation and Sensorimotor Gating in Schizophrenia and Related Animal Models
Geyer, M. A., & BRAFF, D. L. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.4.643 · Cited by 411 · see citing works
Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains
Markel, P. D., Shu, P., Ebeling, C., Carlson, G. A., Nagle, D. L., Smutko, J. S., & Moore, K. J. (1997) · Nature Genetics · doi:10.1038/ng1197-280 · Cited by 401 · see citing works
Inbred strain differences in prepulse inhibition of the mouse startle response
Paylor, R. E., & Crawley, J. N. (1997) · Psychopharmacology · doi:10.1007/s002130050333 · Cited by 382 · see citing works
Owen, E. H., Logue, S. F., Rasmussen, D. L., & Wehner, J. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00165-6 · Cited by 347 · see citing works
GENE DISCOVERY INDROSOPHILA: New Insights for Learning and Memory
Dubnau, J., & Tully, T. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.407 · Cited by 336 · see citing works
Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster
Nuzhdin, S. V., PASYUKOVA, E. G., Dilda, C. L., Zeng, Z., & Mackay, T. F. C. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9734 · Cited by 324 · see citing works
Quantitative Trait Loci Involved in Genetic Predisposition to Acute Alcohol Withdrawal in Mice
Buck, K. J., Metten, P., Belknap, J. K., & Crabbe, J. C. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-10-03946.1997 · Cited by 269 · see citing works
Acoustic and Temporal Factors in the Evocation of Startle
Hoffman, H. S., & Searle, J. L. (1968) · The Journal of the Acoustical Society of America · doi:10.1121/1.1910776 · Cited by 253 · see citing works
Benzer, S. (1971) · PubMed · doi:10.5281/zenodo.10735825 · Cited by 231 · see citing works
High-resolution mapping of quantitative trait loci in outbred mice
Talbot, C. J., Nicod, A., Cherny, S. S., Fulker, D. W., Collins, A. C., & Flint, J. (1999) · Nature Genetics · doi:10.1038/6825 · Cited by 220 · see citing works
Kash, S. F., Tecott, L. H., Hodge, C. W., & Bækkeskov, S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1698 · Cited by 216 · see citing works
Logue, S. F., Owen, E. H., Rasmussen, D. L., & Wehner, J. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00164-4 · Cited by 213 · see citing works
Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder
Morgan, C. A., Grillon, C., Southwick, S. M., Davis, M. E., & Charney, D. S. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.1.64 · Cited by 206 · see citing works
Structure of the mouse behaviour on the elevated plus-maze test of anxiety
Fernández‐Espejo, E. (1997) · Behavioural Brain Research · doi:10.1016/s0166-4328(96)02245-0 · Cited by 189 · see citing works
Using Knockout and Transgenic Mice to Study Neurophysiology and Behavior
Picciotto, M. R., & Wickman, K. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.4.1131 · Cited by 185 · see citing works
Quantitative trait locus analysis of contextual fear conditioning in mice
Wehner, J. M., Radcliffe, R. A., Rosmann, S. T., Christensen, S. C., Rasmussen, D. L., Fulker, D. W., & Wiles, M. (1997) · Nature Genetics · doi:10.1038/ng1197-331 · Cited by 163 · see citing works
Quantitative trait loci analysis affecting contextual conditioning in mice
Caldarone, B. J., Saavedra, C., Tartaglia, K., Wehner, J. M., Dudek, B. C., & Flaherty, L. A. (1997) · Nature Genetics · doi:10.1038/ng1197-335 · Cited by 148 · see citing works
Genetics of nicotine response in four inbred strains of mice
Marks, M. J., Burch, J. B., & Collins, A. C. (1983) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21452-5 · Cited by 140 · cited 1× · see citing works
“…been used extensively as an indicator of ataxic effects for both genetically altered mice (Brandon et al. 1998; Rubinstein et al. 1997) and in response to a variety of substances including ethanol (Schafer and Crabbe 1996), benzodiazepines (Stinchcomb et al. 1989), and nicotine (Marks et al. 1983).”
BackgroundPilz, P. K. D., & Schnitzler, H.-U. (1996) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1996.0044 · Cited by 130 · see citing works
Confirmation of Quantitative Trait Loci for Alcohol Preference in Mice
Tarantino, L. M., McClearn, G. E., Rodriguez, L. A., & Plomin, R. J. (1998) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1998.tb03707.x · Cited by 125 · see citing works
Self-citationMogil, J. S., Richards, S. P., O’Toole, L. A., Helms, M. L., Mitchell, S. R., Kest, B., & Belknap, J. K. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-20-07995.1997 · Cited by 117 · see citing works
Functional Genomics in the Mouse: Phenotype-Based Mutagenesis ScreensPreprint
Schimenti, J. C., & Bućan, M. (1998) · Genome Research · doi:10.1101/gr.8.7.698 · Cited by 95 · see citing works
Acoustic startle threshold of the albino rat (Rattus norvegicus).
Pilz, P. K. D., Schnitzler, H., & Menne, D. (1987) · Journal of comparative psychology · doi:10.1037//0735-7036.101.1.67 · Cited by 69 · see citing works
McNamara, R. K., Stumpo, D. J., Morel, L. M., Lewis, M. H., Wakeland, E. K., Blackshear, P. J., & Lenox, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14517 · Cited by 67 · see citing works
Random Mutagenesis Screen for Dominant Behavioral Mutations in Mice
Nolan, P. M., Kapfhamer, D., & Bućan, M. (1997) · Methods · doi:10.1006/meth.1997.0545 · Cited by 67 · see citing works
A major influence of sex-specific loci on alcohol preference in C57Bl/6 and DBA/2 inbred mice
Peirce, J. L., Derr, R. L., Shendure, J., et al. (1998) · Mammalian Genome · doi:10.1007/s003359900904 · Cited by 65 · see citing works
Willott, J. F., & Bross, L. S. (1996) · Developmental Brain Research · doi:10.1016/0165-3806(95)00188-3 · Cited by 63 · see citing works
Paslawski, T., Treit, D., Baker, G. B., George, M. C., & Coutts, R. T. (1996) · Psychopharmacology · doi:10.1007/bf02805970 · Cited by 52 · see citing works
The use of null mutant mice to study complex learning and memory processes
Wehner, J. M., Bowers, B. J., & Paylor, R. E. (1996) · Behavior Genetics · doi:10.1007/bf02359386 · Cited by 39 · see citing works
Stinchcomb, A. L., Bowers, B. J., & Wehner, J. M. (1989) · Alcohol · doi:10.1016/0741-8329(89)90006-2 · Cited by 27 · see citing works
Panic disorder: Genetic considerations
Crowe, R. (1990) · Journal of Psychiatric Research · doi:10.1016/0022-3956(90)90044-q · Cited by 23 · see citing works
Sensitivity to Ethanol‐Induced Ataxia in HOT and COLD Selected Lines of Mice
Schafer, G. L., & Crabbe, J. C. (1996) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1996.tb01705.x · Cited by 17 · see citing works
Freedman, R. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00271-6 · Cited by 9 · see citing works
Single genes and complex phenotypes
Low, M. J., Kelly, M. A., Rubinstein, M., et al. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000455 · Cited by 8 · see citing works
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Cryan, J. F., Mombereau, C., & Vassout, A. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.009 · Cited by 1,674 · see citing works
Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains
MOY, S., NADLER, J., YOUNG, N., PEREZ, A., HOLLOWAY, L., BARBARO, R., BARBARO, J., WILSON, L., THREADGILL, D., & LAUDER, J. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.07.030 · Cited by 776 · see citing works
Cryan, J. F., & Mombereau, C. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001457 · Cited by 616 · see citing works
Sankoorikal, G. M. V., Kaercher, K. A., Boon, C. J., Lee, J. K., & Brodkin, E. S. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.026 · Cited by 231 · see citing works
Custer, S. K., Neumann, M., Lu, H., Wright, A. C., & Taylor, J. P. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq050 · Cited by 204 · see citing works
Bothe, G. W. M., Bolivar, V. J., Vedder, M. J., & Geistfeld, J. G. (2004) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2004.00064.x · Cited by 131 · see citing works
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Schoch, H., Kreibich, A. S., Ferri, S. L., White, R. S., Bohorquez, D., Banerjee, A., Port, R. G., Dow, H. C., Cordero, L., Pallathra, A. A., et al. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.06.008 · Cited by 92 · see citing works
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Self-citationWilking, J. A., Hesterberg, K. G., Nguyen, V. H., Cyboron, A. P., Hua, A. Y., & Stitzel, J. A. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.05.022 · Cited by 25 · see citing works
- Authors
- Tarantino, L. M., Gould, T. J., Druhan, J. P., & Bucan, M.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Mammalian Genome
- Published
- 2000-07
- Volume
- 11
- Issue
- 7
- Pages
- 555-564
- ISSN
- 0938-8990 (ISSN-L)
- 1432-1777
- OpenAlex
- W1964871934
- Cited by
- 158
- References
- 52
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 6
- FWCI
- 24.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Mammalian Genome (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh057855-04, 7r01da010088-03, 5r01ar045325-04)
- National Institute of Mental Health (MH 57855)
- National Institute on Drug Abuse (DA10088)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR45325-02)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Genetic and Mutation Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- inbred mouse strains, baseline behavior, strain differences, sex differences, motor coordination, rotarod test, anxiety, elevated zero maze, acoustic startle response, habituation, endophenotypes, gene mapping, C57BL/6J mice, DBA/2J, 129/Sv mice
- MeSH terms
- Animals, Behavior, Animal, Chromosome Mapping, Female, Genetic Testing, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Inbred Strains, Motor Activity, Sex Factors, Species Specificity, Reflex, Startle, Time Factors, Mutagenesis, Maze Learning, Mice
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