Abstract
In the current study, we searched for quantitative trait loci (QTL) responsible for a conditioned taste aversion (CTA) measured as a decrease in the intake of a saccharin conditioned stimulus followed by an i.p. injection of 0.15 M LiCl (lithium chloride) (2 ml/100 g body weight). A genome scanning for QTL associated with CTA was performed in the HXB/BXH sets of recombinant inbred (RI) strains derived from the Brown Norway (BN-Lx) rat and the spontaneously hypertensive rat (SHR). The BN-Lx progenitor showed a significantly stronger CTA (8.3 ± 2.8%) than the SHR progenitor (27.8 ± 3.3%, p < .0001). The distribution of CTA values among RI strains was continuous, suggesting a polygenic mode of inheritance. Genome scanning of RI strains with more than 700 gene markers revealed a significant association of CTA with the D2Cebr11s4 marker on chromosome 2 (LRS = 22.7) and with the D4Cebrp149s8 marker on chromosome 4 (LRS = 23.4). The chromosome 2 putative QTL was confirmed by detecting a significant difference in CTA between the SHR progenitor (27.8 ± 3.3%) and the SHR-2 (SHR.BN-D2Rat171/D2Arb24) congenic strain (13.1 ± 4.4%, p < .01) that are genetically identical except for a segment of chromosome 2 that was transferred onto the genetic background of the SHR from the BN strain.
Similar content being viewed by others
REFERENCES
Aitman, T. J., Gotoda, T., Evans, A. L., Imrie, H., Heath, K., Trembling, P., Truman, H., Wallace, C., Doré, C., Flint, J., Kren, V., Kurtz, T. W., Zidek, V., Pravenec, M., and Scott, J. (1997). Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats. Nature Genet. 16:197–201.
Bailey, D. W. (1981). Recombinant and bilineal congenic strains. In Foster, H. L., Small, J. D., and Fox, J. D. (eds.), The Mouse in Biological Research. 1. History, Genetics and Wild Mice, Academic Press, New York, pp. 223–229.
Bottger, A., van Lith, H. A., Křen, V., Křenová, D., Bílá, V., Vorlícek, J., Zídek, V., Musilová, A., Zdobinská, M., Wang, J.-M., van Zutphen, L. F. M., Kurtz, T. W., and Pravenec, M. (1996). Quantitative trait loci influencing cholesterol and phospholipid phenotypes map to chromosomes that contain genes regulating blood pressure in the spontaneously hypertensive rat. J. Clin. Invest. 98:856–862.
Brown, D. M., Matise, T. C., Koike, G., Simon, J. S., Winer, E. S., Zangen, S., McLaughlin, M. G., Shiozawa, M., Atkinson, O. S., Hudson, J. R., Jr., Chakravarti, A., Lander, E. S., and Jacob, H. J. (1998). An integrated genetic linkage map of the laboratory rat. Mamm. Genome 9:521–530.
Buck, K. J., Metten, P., Belknap, J. K., and Crabbe, J. C. (1997). Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J. Neurosci. 17:3946–3955.
Bureš, J., Burešová, O., and Křivánek, J. (1988). Brain and Behavior. Paradigms for Research in Neural Mechanism, Academia, Prague.
Bureš, J., Bermudez-Rattoni, F., and Yamamoto, T. (1998). Conditioned taste aversion. Memory of a special kind. Oxford Psychology Series, vol. 31, Oxford University Press, New York.
Doerge, R. W., and Churchill, G. A. (1996). Permutation tests for multiple loci affecting a quantitative character. Genetics 142:285–294.
Elkins, R. L., Walters, P. A., and Orr, T. E. (1992). Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats. Alcohol Clin. Exp. Res. 16:928–934.
Garcia, J., Ervin, F. R., and Koelling, A. R. (1955). Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122:157–158.
Haley, C. S., and Knott, S. A. (1992). A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69:315–324.
Kren, V., Bila, V., Kasparek, R., Krenova, D., Pravenec, M., and Rapp, K. (1996). Recombinant inbred and congenic strains of the rat for genetic analysis of limb morphogenesis. Folia Biol. (Praha) 42:163–170.
Lander, E. S., and Botstein, D. (1989). Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185–199.
Lander, E. S., and Kruglyak, L. (1995). Genetic dissection of complex traits: Guidelines for interpreting and reporting linkage results. Nature Genet. 11:241–247.
Manly, K., and Olson, M. J. (1999). Overview of QTL mapping software and introduction to Map Manager QT. Mamm. Genome 10:327–334.
Orr, T. E., Walters, P. A., Carl, G. F., and Elkins, R. L. (1993). Brain levels of amines and amino acids in taste aversion-prone and-resistant rats. Physiol. Behav. 53:495–500.
Plomin, R., and McClearn, G. E. (1993). Quantitative trait loci (QTL) analyses and alcohol-related behaviors. Behav. Genet. 23:197–211.
Pravenec, M., Klír, P., Křen, V., Zicha, J., and Kuneš, J. (1989). An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J. Hypertens. 7:217–222.
Pravenec, M., Gauguier, D., Schott, J.-J., Buard, J., Křen, V., Bílá, V., Szpirer, C., Szpirer, J., Wang, J.-M., Huang, H., St. Lezin, E., Spence, M. A., Floodman, P., Printz, M., Lathrop, M., Vergnaud, G., and Kurtz, T. W. (1995). Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains, J. Clin. Invest. 96:1973–1978.
Pravenec, M., Gauguier, D., Schott, J.-J., Buard, J., Křen, V., Bílá, V., Szpirer, C., Szpirer, J., Wang, J.-M., Huang, H., St. Lezin, E., Spence, M. A., Floodman, P., Printz, M., Lathrop, M., Vergnaud, G., and Kurtz, T. W. (1996). A genetic linkage map of the rat derived from recombinant inbred strains, Mamm. Genome 7:117–127.
Pravenec, M., Křen, V., Křenová, D., Bílá, V., Zídek, V., Musilová, A., Van Lith, H. A., and Van Zutphen, L. F. M. (1999). HXB/Ipcv and BXH/Cub recombinant inbred strains of the rat: Strain distribution patterns of 632 alleles. Folia Biol. (Praha) 45:203–215.
Risinger, F. O., and Brown, M. M. (1996). Genetic differences in nicotine-induced conditioned taste aversion. Life Sci. 58:223–229.
Risinger, F. O., and Cunningham, C. L. (1995). Genetic differences in ethanol-induced conditioned taste aversion after ethanol pre-exposure. Alcohol 12:535–539.
Risinger, F. O., and Cunningham, C. L. (1998). Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice. Alcohol. Clin. Exp. Res. 22:1234–1244.
Serikawa, T., Kuramoto, T., Hilbert, P., Mori, M., Yamada, J., Dubay, C. J., Lindpainter, K., Ganten, D., Guenet, J. L., and Lathrop, G. M. (1992). Rat gene mapping using PCR-analyzed microsatellites. Genetics 131:701–721.
Steen, R. G., Kwitek-Black, A. E., Glenn, C., Gullings-Handley, J., Van Etten, W., Atkinson, O. S., Appel, D., Twigger, S., Muir, M., Mull, T., Granados, M., Kissebah, M., Russo, K., Crane, R., Popp, M., Peden, M., Matise, T., Brown, D. M., Lu, J., Kingsmore, S., Tonellato, P. J., Rozen, S., Slonim, D., Young, P., Knoblauch, M., Provoost, A., Ganten, D., Colman, S. D., Rothberg, J., Lander, E. S., and Jacob, H. J. (1999). A high density integrated genetic and radiation hybrid map of the laboratory rat. Genome Res. 9:AP1–AP8.
Thiele, T. E., Van Dijk, G., Campfield, L. A., Smith, F. J., Burn, P., Woods, S. C., Bernstein, I. L., and Seeley, R. J. (1997). Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats. Am. J. Physiol. 272:R726–R730.
Woods, S. C., Figlewicz, D. P., Madden, L., Porte, D., Jr., Sipols, A. J., and Seeley, R. J. (1998). NPY and food intake: Discrepancies in the model. Regul. Pept. 75–76:403–408.
Yamamoto, T., Nagai, T., Shimura, T., and Yasoshima, Y. (1998). Roles of chemical mediators in the taste system. Jpn. J. Pharmacol. 76:325–348.
Zha, H., Wilder, R. L., Goldmuntz, E. A., Cash, J. M., Crofford, L. J., Mathern, P., and Remmers, E. F. (1993). Linkage map of 10 polymorphic markers on rat chromosome 2. Cytogenet. Cell Genet. 63:117–123.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bielavská, E., Kren, V., Musilová, A. et al. Genome Scanning of the HXB/BXH Sets of Recombinant Inbred Strains of the Rat for Quantitative Trait Loci Associated with Conditioned Taste Aversion. Behav Genet 32, 51–56 (2002). https://doi.org/10.1023/A:1014407928865
Issue Date:
DOI: https://doi.org/10.1023/A:1014407928865