Behavior Genetics

, Volume 27, Issue 3, pp 201–210 | Cite as

Mapping Quantitative Trait Loci for Open-Field Behavior in Mice

  • Howard K. Gershenfeld
  • Paul E. Neumann
  • Chantal Mathis
  • Jacqueline N. Crawley
  • Xiaohua Li
  • Steven M. Paul
Article

Abstract

By performing a whole genome screen in an F2 intercross of two strains of mice (A/J and C57BL/6J), which differ markedly in their behavioral response to a brightly lit open field (O-F), we have mapped several quantitative trait loci (QTL) for this complex behavioral phenotype. QTL on chromosomes 1 and 10 were identified that affect both initial ambulation in the O-F (initial “response to novelty” ambulation) (lod of 7.1 and 8.8, respectively) and vertical rearings (lod of 4.5 and 8.5, respectively). For habituated O-F behavior, QTL were identified on chromosomes 3 and 10 for ambulation (lod of 4.1 and 14.7, respectively) and on chromosomes 1, 10, and 19 for vertical rearings (lod of 5.8, 6.0, and 4.7, respectively). The QTL on chromosome 1 (near D1Mit1 16; 101 cM) was specific for initial O-F ambulation behavior, whereas the QTL on chromosome 10 (near D10Mit237; 74 cM) affected both initial and habituated rearing behavior. Additional suggestive QTL (lod, >2.8) were mapped to chromosomes 1, 8, 11, 15, and 19. The QTL on chromosomes 1, 10, and 19 individually explain from 3.2 to 12.7%. Collectively, the multiple independent QTL explain from 16.3 to 24.1% of the F2 population's phe-notypic variance, depending on the trait. These identified QTL should prove useful for dissecting the genetic and behavioral dimensions of O-F behavior, fostering an understanding of individual differences.

Chromosomal mapping quantitative trait loci (QTL) exploratory behavior novelty habituation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Archer, J. (1973). Tests for emotionality in rats and mice: A review. Anim. Behav. 21:205–235.Google Scholar
  2. Bates, J. E., Wachs, T. D., and VandenBos, G. R. (1995). Trends in research on temperament. Psychiatr. Serv. 46:661–663.Google Scholar
  3. Belknap, J. K., Mitchell, S. R., O'Toole, L. A., Helms, M. L., and Crabbe, J. C. (1996). Type I and type II error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains. Behav. Genet. 26:149–160.Google Scholar
  4. Belzung, C. (1992). Hippocampal mossy fibres: implication in novelty reactions or in anxiety behaviours? Behav. Brain Res. 51:149–155.Google Scholar
  5. Berry, R. J., and Bronson, F. H. (1992). Life history and bioeconomy of the house mouse. Biol. Rev. 67:519–550.Google Scholar
  6. Bisaga, A., and Kostowski, W. (1993). Individual behavioral differences and ethanol consumption in Wistar rats. Physiol. Behav. 54:1125–1131.Google Scholar
  7. Blackson, T. C. (1994). Temperament: A salient correlate of risk factors for alcohol and drug abuse. Drug Alcohol Depend. 36:205–214.Google Scholar
  8. Bouchard, T. J. (1994). Genes, environment, and personality. Science 264:1700–1701.Google Scholar
  9. Broadhurst, P. L. (1960). Experiments in psychogenetics: Applications of biometrical genetics to the inheritance of behavior. In Eysenck, H. J. (ed.), Experiments in Personality, Routledge & Kegan Paul, London, Vol. 1, pp. 3–102.Google Scholar
  10. Cerbone, A., and Sadile, A. G. (1994). Behavioral habituation to spatial novelty: Interference and noninterference studies. Neurosci. Biobehav. Rev. 18:497–518.Google Scholar
  11. Cerbone, A., Patacchioli, F. R., and Sadile, A. G. (1993). A neurogenetic and morphogenetic approach to hippocampal functions based on individual differences and neurobehavioral covariations. Behav. Brain Res. 55:1–16.Google Scholar
  12. Cloninger, C. R., Svrakic, D. M., and Przybeck, T. R. (1993). A psychobiological model of temperament and character. Arch. Gen. Psychiatry 50:975–990.Google Scholar
  13. Cohen, R. A. (1993). The Neuropsychology of Attention, Plenum Press, New York.Google Scholar
  14. Crawley, J. N. (1981). Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines. Pharmacol. Biochem. Behav. 15:695–699.Google Scholar
  15. Crawley, J., and Goodwin, F. K. (1980). Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav. 13:167–170.Google Scholar
  16. Crusio, W. E., Schwegler, H., Brust, I., and van Abeelen, J. H. (1989a). Genetic selection for novelty-induced rearing behavior in mice produces changes in hippocampal mossy fiber distributions. J. Neurogenet. 5:87–93.Google Scholar
  17. Crusio, W. E., Schwegler, H., and van Abeelen, J. H. (1989b). Behavioral responses to novelty and structural variation of the hippocampus in mice. I. Quantitative-genetic analysis of behavior in the open-field. Behav. Brain Res. 32:75–80.Google Scholar
  18. Crusio, W. E., Schwegler, H., and van Abeelen, J. H., (1989c). Behavioral responses to novelty and structural variation of the hippocampus in mice. II. Multivariate genetic analysis. Behav. Brain Res. 32:81–88.Google Scholar
  19. DeFries, J. C. (1969). Pleiotropic effects of albinism on open field behaviour in mice. Nature 221:65–66.Google Scholar
  20. DeFries, J. C., and Hegmann, J. P. (1970). Genetic analysis of open-field behavior. In Lindzey, G., and Thiessen, D. D. (eds.), Contributions to Behavior-Genetic Analysis: The Mouse as a Prototype, Appleton-Century-Crofts, New York, pp. 23–56.Google Scholar
  21. DeFries, J. C., Hegmann, J. P., and Halcomb, R. A. (1974). Response to 20 generations of selection for open-field activity in mice. Behav. Biol. 11:481–495.Google Scholar
  22. Dietrich, W., Katz, H., Lincoln, S. E., Shin, H. S., Friedman, J., Dracopoli, N. C., and Lander, E. S. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131:423–447.Google Scholar
  23. Elston, R. C. (1994). P values, power and pitfalls in the linkage analysis of psychiatric disorders. In Gershon, E. R., and Cloninger, C. R. (eds.) Genetic Approaches to Mental Disorders, American Psychiatric Press, Washington, CD, pp. 3–21.Google Scholar
  24. Farenberg, J. (1992). Psychophysiology of neuroticism and anxiety. In Gale, A., and Eysenck, M. W. (eds.), Handbook of Individual Differences: Biological Perspectives, John Wiley & Sons, Chichester.Google Scholar
  25. Flint, J., Corley, R., DeFries, J. C., Fulker, D. W., Gray, J. A., Miller, S., and Collins, A. C. (1995). A simple genetic basis for a complex psychological trait in laboratory mice. Science 269:1432–1435.Google Scholar
  26. Frankel, W. N., Johnson, E. W., and Lutz, C. M. (1995a). Congenic strains reveal effects of the epilepsy quantitative trait locus, E12, separate from other El loci. Mamm. Genome 6:839–843.Google Scholar
  27. Frankel, W. N., Valenzuela, A., Lutz, C. M., Johnson, E. W., Dietrich, W. F., and Coffin, J. M. (1995b). New seizure frequency Qtl and the complex genetics of epilepsy in El mice. Mamm. Genome 6:830–838.Google Scholar
  28. Fuller, J. L. (1967). Effects of the albino gene upon behaviour of mice. Anim. Behav. 15:467–470. ei]Gershon, E. S., and Cloninger, C. R. (eds.) (1994). Genetic Approaches to Mental Disorders, American Psychopathological Association Series, American Psychiatric Press, Washington, DC.Google Scholar
  29. Glickman, S. E., and Morrison, B. J. (1969). Some behavioral and neural correlates of predation susceptibility in mice. Commun. Behav. Biol. 4:261–267.Google Scholar
  30. Gonzalez, J. J. (1994). Neuropsychology of temperament. In Vernon, P. D. (ed.), The Neuropsychology of Individual Differences, Academic Press, San Diego, pp. 235–256.Google Scholar
  31. Gray, J. A. (1987). The Psychology of Fear and Stress, Cambridge University Press, Cambridge.Google Scholar
  32. Hall, C. S. (1938). The inheritance of emotionality. Sigma Xi Q. 26:17–27.Google Scholar
  33. Hausheer-Zarmakupi, Z., Wolfer, D. P., Leisinger-Trigona, M-C., and Lipp, H. P. (1996). Selective breeding for extremes in open-field activity of mice entails a differentiation of hippocampal mossy fibers. Behav. Genet. 26:167–176.Google Scholar
  34. Jacob, H. J., Lindpaintner, K., Lincoln, S. E., Kusumi, K., Bunker, R. K., Mao, Y. P., Ganten, D., Dzau, V. J., and Lander, E. S. (1991). Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67:213–224.Google Scholar
  35. Kagan, J., Reznick, J. S., and Snidman, N. (1988). Biological bases of childhood shyness. Science 240:167–171.Google Scholar
  36. Lander, E., and Kruglyak, L. (1995). Genetic dissection of complex traits—Guidelines for interpreting and reporting linkage results. Nat. Genet. 11:241–247.Google Scholar
  37. Lander, E. S., Green, P., Abrahamson, J., Barlow, A., Daley, M., Lincoln, S., and Newburg, L. (1987). MAPMAKER: An interactive package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1:174–181.Google Scholar
  38. Lassalle, J. M., Halley, H., and Roullet, P. (1994). Analysis of behavioral and hippocampal variation in congenic albino and pigmented B ALB mice. Behav. Genet. 24:161–169.Google Scholar
  39. Lat, J. (1972). The analysis of habituation. Acta Neurobiol. Exp. 33:771–789.Google Scholar
  40. Lincoln, S., and Lander, E. S. (1992). Systematic detection of errors in genetic linkage data. Genomics 14:604–610.Google Scholar
  41. Mathis, C., Paul, S. M., and Crawley, J. N. (1994). Characterization of benzodiazepine-sensitive behaviors in the A/J and C57BL/6J inbred strains of mice. Behav. Genet. 24:171–180.Google Scholar
  42. Mathis, C., Neumann, P. E., Gershenfeld, H., Paul, S. M., and Crawley, J. N. (1995). Analysis of anxiety-related behaviors and responses to benzodiazepine-related drugs in A × B and B × A recombinant inbred mouse strains. Behav. Genet. 25:557–568.Google Scholar
  43. McCleam, G. E. (1959). The genetics of mouse behavior in novel situations. J. Comp. Physiol. Psychol. 52:62–67.Google Scholar
  44. McInnes, L. A., and Freimer, N. B. (1995). Mapping genes for psychiatric disorders and behavioral traits. Curr. Opin. Genet. Dev. 5:376–381.Google Scholar
  45. Neumann, P. E., Frankel, W. N., Letts, V. A., Coffin, J. M., Copp, A. J., and Bernfield, M. (1994). Multifactorial inheritance of neural tube defects: Localization of the major gene and recognition of modifiers in ct mutant mice. Nat. Genet. 6:357–362.Google Scholar
  46. Ossenkopp, K. P., and Mazmanian, D. S. (1985). The measurement and integration of behavioral variables: Aggregation and complexity as important issues. Neurobehav. Toxicol. Teratol. 7:95–100.Google Scholar
  47. Ossenkopp, K. P., Macrae, L. K., and Teskey, G. C. (1987). Automated multivariate measurement of spontaneous motor activity in mice: Time course and reliabilities of the behavioral measures. Pharmacol. Biochem. Behav. 27:565–568.Google Scholar
  48. Paterson, A. H., Damon, S., Hewitt, J. D., Zamir, D., Rabinowitch, H. D., Lincoln, S. E., Lander, E. S., and Tanksley, S. D. (1991). Mendelian factors underlying quantitative traits in tomato: Comparison across species, generations, and environments. Genetics 127:181–197.Google Scholar
  49. Piazza, P. V., Deminiere, J. M., Le, M. M., and Simon, H. (1989). Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513.Google Scholar
  50. Plomin, R., Owen, M. J., and McGuffin, P. (1994). The genetic basis of complex human behaviors. Science 264:1733–1739.Google Scholar
  51. Risch, N., and Botstein, D. (1996). A manic depressive history. Nat. Genet. 12:351–353.Google Scholar
  52. Simmel, E. C., and Bagwell, M. (1983). Genetics of exploratory behavior and activity. In Fuller, J. L., and Simmel, E. C. (eds.), Behavior Genetics: Principles and Applications, Lawrence Erlbaum, Hillsdale, NJ, pp. 89–115.Google Scholar
  53. Smith, R. H., and Connor, J. L. (1974). The inheritance of behavioral wildness in house mice. Anim. Learn. Behav. 2:249–258.Google Scholar
  54. Sokal, R. R., and Rohlf, F. J. (1995). Biometry, W. H. Freeman, New York.Google Scholar
  55. Southwick, C. H., and Clark, L. H. (1966). Aggressive behavior and exploratory activity in fourteen mouse strains. Am. Zool. 6:559.Google Scholar
  56. Stone, C. P. (1932). Wildness and savageness in rats of different strains. In Lashley, K. S. (ed.), Studies in the Dynamics of Behavior, University of Chicago Press, Chicago, pp. 1–55.Google Scholar
  57. Streng, J. (1974). Exploration and learning behavior in mice selectively bred for high and low levels of activity. Behav. Genet. 4:191–204.Google Scholar
  58. Suarez, S. D., and Gallup, G. G. (1982). Open-field behavior in chickens: The experimenter is a predator. J. Comp. Physiol. Psych. 96:432–439.Google Scholar
  59. Tarter, R. E., and Vanyukoy, M. (1994). Alcoholism: A developmental disorder. J. Consult. Clin. Psychol. 62:1096–1107.Google Scholar
  60. Thompson, W. R. (1956). The inheritance of behavior: Activity differences in five inbred mouse strains. J. Hered. 47:147–148.Google Scholar
  61. Thompson, W. R. (1957). Traits, factors, and genes. Eugen. Q. 4:8–16.Google Scholar
  62. Turunen, M. (1988). Trends in temperament research. Acta Paediatr. 7:81–86.Google Scholar
  63. van Abeelen, J. H. (1975). Genetic analysis of behavioural responses to novelty in mice. Nature 254:239–241.Google Scholar
  64. van Abeelen, J. H. (1989). Genetic control of hippocampal cholinergic and dynorphinergic mechanisms regulating novelty-induced exploratory behavior in house mice. Experientia 45:839–845.Google Scholar
  65. Walsh, R. N., and Cummins, R. A. (1976). The open-field test: A critical review. Psychol. Bull. 83:482–504.Google Scholar
  66. Watson, D., Clark, L. A., and Harkness, A. R. (1994). Structures of personality and their relevance to psychopathology. J. Abnorm. Psychol. 103:18–31.Google Scholar
  67. Wills, T. A., DuHamel, K., and Vaccaro, D. (1995). Activity and mood temperament as predictors of adolescent substance use: Test of a self-regulation mediational model. J. Pers. Soc. Psychol. 68:901–916.Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Howard K. Gershenfeld
    • 1
  • Paul E. Neumann
    • 2
  • Chantal Mathis
    • 3
  • Jacqueline N. Crawley
    • 4
  • Xiaohua Li
    • 1
  • Steven M. Paul
    • 5
    • 6
  1. 1.Department of PsychiatryUniversity of Texas Southwestern Medical CenterDallas
  2. 2.Department of Anatomy & NeurobiologyUniversity of DalhousieHalifaxCanada
  3. 3.Laboratorie de Psychophysiologie, URA-CNRS 1295Universite Louis PasteurStrasbourgFrance
  4. 4.NIMH, NIHExperimental Therapeutics BranchBethesda
  5. 5.Lilly Research LaboratoryIndianapolis
  6. 6.Departments of Psychiatry, Pharmacology and ToxicologyIndiana University School of MedicineIndianapolis

Personalised recommendations