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Mapping quantitative trait loci for nicotine preference in mice

Journal Article


Abstract


  • Tobacco smoke contains a number of toxic substances which contribute to the toxic effects of smoking, but dependence seems to be caused by the positive and negative reinforcing properties of the main component nicotine. In order to study the genetic basis of nicotine dependence we used a QTL mapping approach in mice. Inbred strains of mice were tested for nicotine preference using a two bottle choice paradigm as described by Robinson et al (Psychopharmacology 1996, 124:332). The two strains representing extreme phenotypes C57BL/6 (B6) for high nicotine consuming (HNC) and ST/bJ for low nicotine consuming (LNC) were crossed and the resulting F1 generation intercrossed to generate 497 mice of a F2 generation. Initially 46 LNC and 47 HNC mice of F2 were genotyped using 102 microsatellite markers distributed equally across the genome and analyzed by chi2 test. An overrepresentation of B6 alleles was seen in the HNC group for marker D7MIT178 (p =.001) on the tip of chromosome 7. The region was analyzed in more detail by genotyping the whole F2 sample and calculating LOD scores using MAPMAKER/QTL. The maximum LOD score was 2.88 and was mainly due to the females which produced a LOD score of 3.35 when analyzed separately. The area contains the mouse cytochrome P450 gene cluster. The human CYP2A6 gene is involved in nicotine metabolism and may play a role in nicotine dependence. Suggestive evidence for additional provisional QTLs was obtained on chromosome 11 (LOD = 2.7), chr. 3 (LOD = 1.2), and chr. 18 (LOD = 1.2).

Publication Date


  • 2001

Citation


  • Wildenauer, D. B., Aschoff, S., Hallmayer, J., Schwab, S. G., Gabel, S., Schroff, K. C., & Richter, E. (2001). Mapping quantitative trait loci for nicotine preference in mice. American Journal of Medical Genetics - Neuropsychiatric Genetics, 105(7), 568.

Scopus Eid


  • 2-s2.0-33749092779

Web Of Science Accession Number


Start Page


  • 568

Volume


  • 105

Issue


  • 7

Abstract


  • Tobacco smoke contains a number of toxic substances which contribute to the toxic effects of smoking, but dependence seems to be caused by the positive and negative reinforcing properties of the main component nicotine. In order to study the genetic basis of nicotine dependence we used a QTL mapping approach in mice. Inbred strains of mice were tested for nicotine preference using a two bottle choice paradigm as described by Robinson et al (Psychopharmacology 1996, 124:332). The two strains representing extreme phenotypes C57BL/6 (B6) for high nicotine consuming (HNC) and ST/bJ for low nicotine consuming (LNC) were crossed and the resulting F1 generation intercrossed to generate 497 mice of a F2 generation. Initially 46 LNC and 47 HNC mice of F2 were genotyped using 102 microsatellite markers distributed equally across the genome and analyzed by chi2 test. An overrepresentation of B6 alleles was seen in the HNC group for marker D7MIT178 (p =.001) on the tip of chromosome 7. The region was analyzed in more detail by genotyping the whole F2 sample and calculating LOD scores using MAPMAKER/QTL. The maximum LOD score was 2.88 and was mainly due to the females which produced a LOD score of 3.35 when analyzed separately. The area contains the mouse cytochrome P450 gene cluster. The human CYP2A6 gene is involved in nicotine metabolism and may play a role in nicotine dependence. Suggestive evidence for additional provisional QTLs was obtained on chromosome 11 (LOD = 2.7), chr. 3 (LOD = 1.2), and chr. 18 (LOD = 1.2).

Publication Date


  • 2001

Citation


  • Wildenauer, D. B., Aschoff, S., Hallmayer, J., Schwab, S. G., Gabel, S., Schroff, K. C., & Richter, E. (2001). Mapping quantitative trait loci for nicotine preference in mice. American Journal of Medical Genetics - Neuropsychiatric Genetics, 105(7), 568.

Scopus Eid


  • 2-s2.0-33749092779

Web Of Science Accession Number


Start Page


  • 568

Volume


  • 105

Issue


  • 7