Genetic predisposition to lymphomas in mice

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Abstract
The spontaneous mouse lymphoma is a model of multlfactorial genetic disease. It is induced by the endogenous murlne leukemia vlrus (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 pried 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 9‐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 identlfied 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 posslble relevance of Tlsm‐1 in this step, is discussed. The length of the latent period is determined by a gene Ua‐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 straln, two resistance genes, Msmr‐1 (Chr. 17) and Msmr‐2 (Chr. 18), have been identified. In SL/Kh, all of these host genetic and epigenetlc factors are favorable for lymphoma development. This model Offem 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.

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