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Gene interaction and single gene effects in colon tumour susceptibility in mice

Nature Genetics volume 14, pages 468–470 (1996)Cite this article

Abstract

To dissect the multigenic control of colon tumour susceptibility in the mouse1 we used the set of 20 CcS/Dem (CcS) recombinant congenic (RC) strains2. Each CcS strain carries a unique, random subset of approximately 12.5% of the genome of strain STS/A (STS) on the genetic background of BALB/cHeA (BALB/c)3. Previously, applying a protocol of 26 injections of 1,2-dimethylhydrazine (DMH), we detected two susceptibility loci, Scc1 and Scc2, on chromosome 2 (refs 4, 5). Using a shorter tumour-induction procedure, combining DMH and N-ethyl-N-nitrosourea (ENU) treatment, we demonstrate that BALB/c, STS and most CcS strains are relatively resistant. The strain CcS-19, however, is susceptible, probably due to a combination of BALB/c and STS alleles at several loci. Analysis of 192 (BALB/c × CcS-19) F2 mice revealed, in addition to the Scc1/Scc2 region, three new susceptibility loci: Scc3 on chromosome 1, Scc4 on chromosome 17 and Scc5 on chromosome 18. Scc4 and Scc5 have no apparent individual effect, but show a strong reciprocal interaction. Their BALB/c and STS alleles are not a priori susceptible or resistant but the genotype at one locus determines the effect of the allele at the second locus and vice versa. These findings and the accompanying paper on lung tumour susceptibility6 show that interlocus interactions are likely to be an important component of tumour susceptibility.

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Authors and Affiliations

  1. Divisions of Molecular Genetics, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands

    Tom van Wezel, Alphons P.M. Stassen, Corina J.A. Moen, Martin A. van der Valk & Peter Demant

  2. Radiothempy of the Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands

    Augustinus A.M. Hart

Authors
  1. Tom van Wezel
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  2. Alphons P.M. Stassen
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  3. Corina J.A. Moen
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  4. Augustinus A.M. Hart
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  5. Martin A. van der Valk
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  6. Peter Demant
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Correspondence to Peter Demant.

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Wezel, T., Stassen, A., Moen, C. et al. Gene interaction and single gene effects in colon tumour susceptibility in mice. Nat Genet 14, 468–470 (1996). https://doi.org/10.1038/ng1296-468

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