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The recombinant congenic strains—a novel genetic tool applied to the study of colon tumor development in the mouse

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Abstract

The development of tumors in mice is under multigenic control, but, in spite of considerable efforts, the identification of the genes involved has so far been unsuccessful, because of the insufficient resolution power of the available genetic tools. Therefore, a novel genetic tool, the RC (Recombinant Congenic) strains system, was designed. In this system, a series of RC strains is produced from two inbred strains, a “background” strain and a “donor” strain. Each RC strain contains a different small subset of genes from the donor strain and the majority of genes from the background strain. As a consequence, the individual genes of the donor strain which are involved in the genetic control of a multigenic trait, become separated into different RC strains, where they can be identified and studied individually. One of the RC strains series which we produced is made from the parental strains BALB/cHeA (background strain) and STS/A (donor strain). We describe the genetic composition of this BALB/cHeA-C-STS/A (CcS/Dem) series and show, using 45 genetic autosomal markers, that it does not deviate from the theoretical expectation. We studied the usefulness of the CcS/Dem RC strains for analysis of the genetics of colon tumor development. The two parental strains, BALB/cHeA and STS/A, are relatively resistant and highly susceptible, respectively, to the induction of colon tumors by 1,2-dimethylhydrazine (DMH). The individual RC strains differ widely in colon tumor development after DMH treatment; some are highly susceptible, while others are very resistant. This indicates that a limited number of genes with a major effect are responsible for the high susceptibility of the STS strain. Consequently, these genes can be mapped by further analysis of the susceptible RC strains. The differences between the RC strains were not limited to the number of tumors, but the RC strains differed also in size of the tumors and the relative susceptibility of the two sexes. Our data indicate that the number of tumors and the size of tumors are not controlled by the same genes. The genetics of these different aspects of colon tumorigenesis can also be studied by the RC strains. The DMH-treated mice of the parental strains and the RC strains also developed anal tumors and haemangiomas in varying numbers. The strain distribution pattern (SDP) of susceptibility for each of the three types of tumors induced by DMH is different, indicating that development of these tumors is under control of different, largely non-overlapping, sets of genes. Thus, with a single series of RC strains, genes involved in tumorigenesis in various organs and tissues can be studied separately. These results indicate that the novel genetic tool, the RC strain system, offers new possibilities for analysis of the multigenic control of tumor development.

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Authors and Affiliations

  1. Division of Molecular Genetics, Antoni van Leeuwenhoek Huis, Amsterdam, the Netherlands

    Corina J. A. Moen, Martin A. van der Valk, Margriet Snoek & Peter Demant

  2. Radiotherapy of The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam, the Netherlands

    Augustinus A. M. Hart

  3. Department of Laboratory Animal Science, Faculty of Veterinary Medicine, State University Utrecht, the Netherlands

    Bert F. M. van Zutphen

  4. Department of Chemical Pathology, Institute of Pathology, Albert-Ludwigs University, Freiburg, Germany

    Otto von Deimling

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  1. Corina J. A. Moen
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  2. Martin A. van der Valk
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  3. Margriet Snoek
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  4. Bert F. M. van Zutphen
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  5. Otto von Deimling
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  6. Augustinus A. M. Hart
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  7. Peter Demant
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Moen, C.J.A., van der Valk, M.A., Snoek, M. et al. The recombinant congenic strains—a novel genetic tool applied to the study of colon tumor development in the mouse. Mammalian Genome 1, 217–227 (1991). https://doi.org/10.1007/BF00352328

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