Genetic predisposition to lymphomas in mice.
The spontaneous mouse lymphoma is a model of multifactorial genetic disease. It is induced by the endogenous murine leukemia virus (MuLV), whose genome is inherited as a Mendelian dominant trait. Lymphoma development takes place in multiple stages affected by many host genetic and epigenetic factors. An inbred strain SL/Kh with a high incidence of pre-B lymphomas has been established and the genetic predisposition of SL/Kh mice to lymphomas is being studied in the crosses with other inbred strains of mice. In the cross to the NFS/N lacking endogenous MuLV genome, it has been shown that lymphomas are induced by the expression of Emv-11 provirus (Chr. 7), and the types of B-lineage lymphomas are determined by combinations of the host genes, Esl-1 (Chr. 17) and Foc-1 (Chr. 4). Another gene, Tlsm-1 (Chr. 7) that determines the type of lymphomas to be T-lineage, is identified in the cross with AKR/Ms, with a high incidence of T-lymphomas. The role of the thymus in the development of T-lymphomas in the mouse, and the possible relevance of Tlsm-1 in this step, is discussed. The length of the latent period is determined by a gene Lia-1 (Chr. 17). A maternal resistance factor that is a maternal antibody to MuLV transmitted via milk and that epigenetically inhibits MuLV expression in SL/Ni-Eco-, one of subline of SL/NI mice, has been shown. Weak but definitive maternal resistance also operates in SL/Ni-Eco+, a subline lacking the maternal antibody to MuLV. In the latter, there is a recessive resistance gene Nir-1 (Chr. 4). In the cross with MSM/Ms, a wild mice-derived inbred strain, two resistance genes, Msmr-1 (Chr. 17) and Msmr-2 (Chr. 18), have been identified. In SL/Kh, all of these host genetic and epigenetic factors are favorable for lymphoma development. This model offers not only an understanding of the pathogenesis of virus-induced lymphomas but also may provide starting material for the comparative approach to homologous human diseases.
Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Japan.
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D000818:Animals; D004198:Disease Susceptibility; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains