Our objectives are the development and genetic characterization of sets of recombinant inbred (RI) strains of mice, which are derived from the crosses of pairs of inbred (progenitor) strains. These RI strains are being used to genetically analyze numerous differences between the progenitors, including lymphoma susceptibility. The RI strains are being typed for newly discovered polymorphisms, which serve as genetic markers for the analysis of inheritance of complex traits such as susceptibility to lymphoma and autoimmunity. The lymphoma incidence and latency has been determined for half of the 26 AKXD RI strains which were inbred from the cross of the high lymphoma strain AKR/J with the low lymphoma DBA/2J strain. Mice from the remaining ADXD strains are currently being aged to determine their predisposition to lymphoma. It is evident that none of the 13 strains are as lymphoma-prone as are AKR/J progenitor strain mice. Although some strains have quite high incidences of lymphoma, the age of onset is later. Similarly, although DBA/2J is a lymphoma-resistant and long-lived strain (average lifespan greater than 700 days), none of the 13 AKXD RI strains appears to have moderate incidences of lymphomas, suggesting that various combinations of genes may interact so as to confer moderate susceptibility to lymphoma. Specific loci which are expected to contribute to AKR/J susceptibility include the ecotropic virogenes Akv-1 and Akv-4, the H-2 haplotype, and the Rmcf locus which controls the spread of MCF-type viruses. The AKXD strains have been characterized with respect to all of these loci. The importance of the Akv virogenes to AKR lymphoma is evident in this material as in previous studies. The most common tumor types were lymphocytic lymphomas and follicle center-cell lymphomas. We are attempting to transfer the xenotropic virus non-inducibility trait of SWR/J (controlled by the Bxv-1 locus) to the AKR/J background. We are using the visible mutation ichthyosis (ic) to select for the Bxv-1 locus indirectly. If successful, we will be able to evaluate the influence of the Bxv-1 locus on susceptibility to lymphoma in the AKR/J mouse strain. RI strains have been used to map restriction-fragment length polymorphisms detected with a serum amyloid A cDNA probe in chromosome 7. Several serum amyloid A genes are evidently located in a tight cluster. (Q)

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National Cancer Institute (NCI)
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Mammalian Genetics Study Section (MGN)
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Jackson Laboratory
Bar Harbor
United States
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