Skip to main content
SpringerLink
Log in

Identification and Time Dependence of Quantitative Trait Loci for Basal Locomotor Activity in the BXD Recombinant Inbred Series and a B6D2 F2 Intercross

  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

A complimentary two-phase strategy was used to detect and map quantitative trait loci (QTLs) associated with the basal locomotor response to a saline challenge (10 ml/kg). In phase 1, putative QTLs, significant at p < 0.01 or better, were identified by analysis of the strain means for 25 strains of the B × D recombinant inbred series. QTLs were identified on chromosomes 1, 3, 5, 9, 10, 16, and 18. Some of these QTLs were detected across the entire experimental period (0–20 min), while others were associated with specific 5-min blocks. Eighteen hundred C57BL/6J (B6) × DBA/2J (D2) F2 intercross animals were phenotyped for the basal locomotor response, and of this group, 500 to 700 individuals, psuedo-randomly selected, were used for a genomewide scan to confirm the RI-generated QTLs and to detect new QTLs. No new QTLs were detected but the QTLs on chromosome 1 were confirmed at p < 10−5 to p < 10−9, depending on the time interval. In addition, the QTLs on chromosomes 5 and 9 were confirmed at p < 0.001, providing a combined probability (RI + F2) which exceeds the threshold for a significant association. Two additional phenotypes which showed significant RI strain differences were examined—adaptation and thigmotaxis. Adaptation mapped to the same region of chromosome 9 and thigmotaxis to the same region of chromosome 1 as the distance-traveled QTL. Overall, the data presented here and elsewhere (Flint et al., 1995; Gershenfeld et al., 1997) illustrate that QTLs for basal activity are both robust and reliable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Archer, J. (1973). Tests for emotionality in rats and mice: A review. Anim.Behav. 21:205-235.

    Google Scholar 

  • Barton, N. H., and Turelli, M. (1989). Evolutionary quantitative genetics: how little do we know? Annu.Rev.Genet. 23:337-370.

    Google Scholar 

  • 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 

  • Bindra, D., and Thompson, W. R. (1953). An evaluation of defecation and urination as measures of fearfulness. J.Comp.Physiol.Psychol. 46:43-45.

    Google Scholar 

  • Buck, K., Metten, P., Belknap, J., and Crabbe, J. (1999). Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and 11. Mammal.Genome 10(5):431-437.

    Google Scholar 

  • Caldarone, B., Saaveda, C., Tartaglia, K., Wehner, J., Dudek, B. C., and Flaherty, L. (1997). Quantitative trait loci analysis affecting contextual conditioning in mice. Nature Genet. 17:335-337.

    Google Scholar 

  • Crabbe, J. C., Kosobud, A., Young, E. R., and Janowsky, J. S. (1983). Polygenic and single-gene determination or responses to ethanol in B × D/Ty recombinant inbred mouse strains. Neurobehav.Toxicol.Teratol. 5:181-187.

    Google Scholar 

  • Crabbe, J. C., Wahlsten, D., and Dudek, B. C. (1999). Genetics of mouse behavior: Interactions with lab environment. Science 284:1245-1247.

    Google Scholar 

  • Crawley, J. N., Belknap, J. K., Collins, A. C., Crabbe, J. C., Frankel, W., Henderson, N., Hitzemann, R. J., Maxson, S. C., Miner, L. L., Silva, A. I., Wehner, J. M., Wynshaw-Boris, A.,and Paylor, R. (1997). Behavioral phenotypes of inbred mouse strains: Implications and recommendations for molecular studies. Psychopharmacology 132:107-124.

    Google Scholar 

  • Cunningham, C. L. (1995). Localization of genes influencing ethanolinduced conditioned place preference and locomotor activity in B × D recombinant inbred mice. Psychopharmacology 120:28-41.

    Google Scholar 

  • DeFries, J. C. (1969). Pleiotropic effects of albinism on open-field behavior in mice. Nature 221:81-88.

    Google Scholar 

  • DeFries, J. C., Gervais, M. C., and Thomas, E. A. (1978). Response to 30 generations of selection for open-field activity in laboratory mice. Behav.Genet. 8:3-13.

    Google Scholar 

  • Demarest, K., McCaughran, J., Jr., Mahjubi, E., Cipp, L., and Hitzemann, R. (1999). Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2. J.Neurosci. 19:549-561.

    Google Scholar 

  • Dietrich, W. F., Miller, J. C., Steen, R. G., et al. (1994). A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7:220-245.

    Google Scholar 

  • Fisher, R. A. (1918). The correlation between relatives on the supposition of Mendelian inheritance. Trans.Roy.Soc.Edinburgh 52:399-433.

    Google Scholar 

  • Flint, J., Corley, R., DeFries, J. C., Fulker, D. W., Gray, J. A., Miller, S., and Collins, A. C. (1995). A simple genetics basis for a complex psychological trait in laboratory mice. Science 269:1432-1435.

    Google Scholar 

  • Fuller, J. L. (1967). Effect of the albino gene on behavior of mice. Anim.Behav. 15:467-470.

    Google Scholar 

  • Gershenfeld, H. K., and Paul, S. M. (1997). Mapping quantitative trait loci for fear-like behavior in mice. Genomics 46(1):1-8.

    Google Scholar 

  • Gershenfeld, H. K., Neumann, P. E., Mathis, C., Crawley, J. N., Li, X., and Paul, S. M. (1997). Mapping quantitative trait loci for open-field behavior in mice. Behav.Genet. 27:201-210.

    Google Scholar 

  • Hall, C. S. (1934). Emotional behavior in the rat. I. Defecation and urination as measures of individual differences in emotionality. J.Comp.Psychol. 18:385-403.

    Google Scholar 

  • Hall, C. S. (1936). Emotional behavior in the rat. III. The relationship emotionality and ambulatory activity. J.Comp.Psychol. 18:385-403.

    Google Scholar 

  • Hitzemann, R., Hitzemann, B., Kanes, S., and Dains, K. (1995). Genetics and organization of the basal ganglia. Int.Rev.Neurobiol. 38:43-94.

    Google Scholar 

  • Hughes, R. N. (1968). Behaviour of male and female rats with a free choice of two environments differing in novelty. Anim.Behav. 16:92-96.

    Google Scholar 

  • Kanes, S., Hitzemann, B., and Hitzemann, R. (1996). Mapping the genes for haloperidol-induced catalepsy. J.Pharmacol.Exp.Ther. 277:1016-1025.

    Google Scholar 

  • Kvist, S. B., and Selander, R. K. (1992). A qualitative aspect fo learning-sensitive open-field ambulation in mice. Scand.J.Psychol. 33:97-107.

    Google Scholar 

  • Lander, E. S., and Botstein, E. (1989). Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185-199.

    Google Scholar 

  • Lander, E., and Kruglyak, L. (1995). Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11:241-247.

    Google Scholar 

  • Lasalle, J. M., Halley, H., and Roullet, P. (1994). Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice. Behav.Genet. 24:161-169.

    Google Scholar 

  • Lynch, M., and Walsh, B. (1997). Genetics and Analysis of Quantitative Traits, Sinauer Associates, Sunderland, MA.

  • Mathis, C., Neumann, P. E., Gershenfeld, H., Paul, S. M., and Crawley, J. N. (1995). Genetic analysis of anxiety-related behaviors and responses to benzodiazepine-related drugs in A × B and B × A recombinant inbred strains. Behav.Genet. 25:557-568.

    Google Scholar 

  • Misslin, R., and Cigrang, M. (1986). Does neophobia necessarily imply fear or anxiety? Behav.Process. 12:45-50.

    Google Scholar 

  • Neiderhiser, J. M., Plomin, R., and McClearn, G. E. (1992). The use of C × B recombinant inbred mice to detect quantitative trait loci in behavior. Physiol.Behav. 52:429-439.

    Google Scholar 

  • Patel, N. V., and Hitzemann, R. (2000). Detection and mapping of quantitative trait loci for haloperidol-induced catalepsy in a C57BL/6J × DBA/2J F2 intercross. Behav.Genet. (in press).

  • Phillips, T. J., Huson, M., Gwiazdon, C., Burkhart-Kasch, S., and Shen, E. H. (1995). Effects of acute and repeated ethanol exposures on the locomotor activity of B × D recombinant inbred mice. Alcohol Clin.Exp.Res. 19:1-10.

    Google Scholar 

  • Phillips, T. J., Huson, M. G., and McKinnon, C. S. (1998). Localization of genes mediating acute and sensitized locomotor responses to cocaine in B × D/Ty recombinant inbred mice. J.Neurosci. 18(8):3023-3034.

    Google Scholar 

  • Plomin, R., McClearn, G. E., Gora-Masalk, G., and Neiderhiser, J. M. (1991). Use of recombinant inbred strains to detect quantitative trait loci associated with behavior. Behav.Genet. 21:99-116.

    Google Scholar 

  • Radcliffe, R. A., Jones, B. C., and Erwin, V. G. (1998). Mapping the provisional quantitative trait loci influencing temporal variation in locomotor activity in LS × SS recombinant inbred strains. Behav.Genet. 28:39-47.

    Google Scholar 

  • Simon, P., Dupuis, R., and Costenin, J. (1994). Thigomotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav.Brain Res. 61:59-64.

    Google Scholar 

  • Soller, M., Brody, T., and Genizi, A. (1976). On the power of experimental designs for the direction of linkage between marker loci and quantitative loci in crosses between inbred lines. Theor.Appl.Genet. 47:35-39.

    Google Scholar 

  • Talbot, C. J., Nicod, A., Cherny, S. S., Fulker, D. W., Collins, A. C., and Flint, J. (1999). High resolution mapping of quantitative trait loci in outbred mice. Nature Genet. 21:305-308.

    Google Scholar 

  • Tarricone, B. I., Hintgen, J. N., Belknap, J. K., Mitchell, S. R., and Nurnberger, J. I., Jr. (1995). Quantitative trait loci associated with the behavioral response of B × D recombinant inbred mice to restraint stress: A preliminary communication. Behav.Genet. 83:489-495.

    Google Scholar 

  • Treit, D., and Fundynus, M. (1988). Thigmotaxis as a test for anxiolytic activity in rats. Pharmacol.Biochem.Behav. 31:959-962.

    Google Scholar 

  • Walsh, R. N., and Cummings, R. A. (1976). The open-field test: A critical review. Psychol.Bull. 83:482-504.

    Google Scholar 

  • Wehner, J. M., Radcliffe, R. A., Rosmann, S. T., Christensen, S. C., Rasmussen, D. L., Fulker, D. W., and Wiles, M. (1997). Quantitative trait locus analysis of contextual fear conditioning in mice. Nature Genet. 17(3):331-334.

    Google Scholar 

  • Welker, W. I. (1957). Free and forced exploration of a novel situation by rats. Psychol.Rep. 3:95-108.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, SUNY of Stony Brook, Stony Brook, New York, 11794-8101

    Jay Koyner, Kristin Demarest, James McCaughran Jr, Laura Cipp & Robert Hitzemann

  2. Department of Neurobiology and Behavior, SUNY at Stony Brook, Stony Brook, New York, 11794-8101

    Kristin Demarest

  3. Research and Psychiatry Services, Veterans Administration Medical Center, Northport, New York, 11768

    Robert Hitzemann

Authors
  1. Jay Koyner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristin Demarest
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James McCaughran Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Laura Cipp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Hitzemann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koyner, J., Demarest, K., McCaughran, J. et al. Identification and Time Dependence of Quantitative Trait Loci for Basal Locomotor Activity in the BXD Recombinant Inbred Series and a B6D2 F2 Intercross. Behav Genet 30, 159–170 (2000). https://doi.org/10.1023/A:1001963906258

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1001963906258

Search

Navigation