Identification of hepatocarcinogen-resistance genes in DBA/2 mice

G H Lee, L M Bennett, R A Carabeo, N R Drinkwater

Research output: Contribution to journalArticle

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Abstract

Male DBA/2J mice are approximately 20-fold more susceptible than male C57BL/6J mice to hepatocarcinogenesis induced by perinatal treatment with N,N-diethylnitrosamine (DEN). In order to elucidate the genetic control of hepatocarcinogenesis in DBA/2J mice, male BXD recombinant inbred, D2B6F1 x B6 backcross, and D2B6F2 intercross mice were treated at 12 days of age with DEN and liver tumors were enumerated at 32 weeks. Interestingly, the distribution of mean tumor multiplicities among BXD recombinant inbred strains indicated that hepatocarcinogen-sensitive DBA/2 mice carry multiple genes with opposing effects on the susceptibility to liver tumor induction. By analyzing D2B6F1 x B6 backcross and D2B6F2 intercross mice for their liver tumor multiplicity phenotypes and for their genotypes at simple sequence repeat marker loci, we mapped two resistance genes carried by DBA/2J mice, designated Hcr1 and -2, to chromosomes 4 and 10, respectively. Hcr1 and Hcr2 resolved the genetic variance in the backcross population well, indicating that these resistance loci are the major determinants of the variance in the backcross population. Although our collection of 100 simple sequence repeat markers allowed linkage analysis for approximately 95% of the genome, we failed to map any sensitivity alleles for DBA/2J mice. Thus, it is likely that the susceptibility of DBA/2J mice is the consequence of the combined effects of multiple sensitivity loci.
Original languageEnglish
Pages (from-to)387-95
Number of pages9
JournalGenetics
Volume139
Issue number1
Publication statusPublished - Jan 1995

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Inbred DBA Mouse
Genes
Diethylnitrosamine
Microsatellite Repeats
Liver
Neoplasms
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 4
Inbred C57BL Mouse
Population
Alleles
Genotype
Genome
Phenotype

Keywords

  • Genetic Linkage
  • Animals
  • Genetic Markers
  • Diethylnitrosamine
  • Drug Resistance
  • Mice
  • Carcinogens
  • Chromosome Mapping
  • Mice, Inbred DBA
  • Polymerase Chain Reaction
  • Mice, Inbred Strains
  • Liver Neoplasms, Experimental
  • Heterozygote
  • Mice, Inbred C57BL
  • Crosses, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Species Specificity
  • Female
  • Male

Cite this

Lee, G. H., Bennett, L. M., Carabeo, R. A., & Drinkwater, N. R. (1995). Identification of hepatocarcinogen-resistance genes in DBA/2 mice. Genetics, 139(1), 387-95.

Identification of hepatocarcinogen-resistance genes in DBA/2 mice. / Lee, G H; Bennett, L M; Carabeo, R A; Drinkwater, N R.

In: Genetics, Vol. 139, No. 1, 01.1995, p. 387-95.

Research output: Contribution to journalArticle

Lee, GH, Bennett, LM, Carabeo, RA & Drinkwater, NR 1995, 'Identification of hepatocarcinogen-resistance genes in DBA/2 mice', Genetics, vol. 139, no. 1, pp. 387-95.
Lee GH, Bennett LM, Carabeo RA, Drinkwater NR. Identification of hepatocarcinogen-resistance genes in DBA/2 mice. Genetics. 1995 Jan;139(1):387-95.
Lee, G H ; Bennett, L M ; Carabeo, R A ; Drinkwater, N R. / Identification of hepatocarcinogen-resistance genes in DBA/2 mice. In: Genetics. 1995 ; Vol. 139, No. 1. pp. 387-95.
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AB - Male DBA/2J mice are approximately 20-fold more susceptible than male C57BL/6J mice to hepatocarcinogenesis induced by perinatal treatment with N,N-diethylnitrosamine (DEN). In order to elucidate the genetic control of hepatocarcinogenesis in DBA/2J mice, male BXD recombinant inbred, D2B6F1 x B6 backcross, and D2B6F2 intercross mice were treated at 12 days of age with DEN and liver tumors were enumerated at 32 weeks. Interestingly, the distribution of mean tumor multiplicities among BXD recombinant inbred strains indicated that hepatocarcinogen-sensitive DBA/2 mice carry multiple genes with opposing effects on the susceptibility to liver tumor induction. By analyzing D2B6F1 x B6 backcross and D2B6F2 intercross mice for their liver tumor multiplicity phenotypes and for their genotypes at simple sequence repeat marker loci, we mapped two resistance genes carried by DBA/2J mice, designated Hcr1 and -2, to chromosomes 4 and 10, respectively. Hcr1 and Hcr2 resolved the genetic variance in the backcross population well, indicating that these resistance loci are the major determinants of the variance in the backcross population. Although our collection of 100 simple sequence repeat markers allowed linkage analysis for approximately 95% of the genome, we failed to map any sensitivity alleles for DBA/2J mice. Thus, it is likely that the susceptibility of DBA/2J mice is the consequence of the combined effects of multiple sensitivity loci.

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KW - Crosses, Genetic

KW - Repetitive Sequences, Nucleic Acid

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KW - Male

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