Recently, we have identified and characterized a recombinant inbred (RI) mouse strain designated BXH-2, that spontaneously expresses a B-tropic MuLV throughout life and has a high incidence of myeloid leukemia. The virus is not present in the germline and is maternally transmitted. Southern analysis using a highly specific ecotropic MuLV DNA-derived probe indicated that 92 independent BXH-2 tumors contained newly acquired tumor- specific proviruses and 25 of these tumors contain only a single detectable tumor-specific provirus. We have molecularly cloned a B-ecotropic BXH-2 tumor specific provirus along with flanking cellular sequences. In addition there appears to be a new common site of virus integration in BXH-2 myeloid tumors that may represent a new cellular proto-oncogene involved in myeloid disease. The BXH-2 strains was the only BXH-strain among twelve, generated by crossing two low leukemic strains (C57BL/6J x C3H/HeJ) to have a high incidence of leukemia; this presents us with a disease model and eleven genotypically distinct controls. We feel that BXH-2 mice represent an important new model system for study of both host and viral factors involved in myeloid leukemogenesis. Specifically utilizing BXH-RI mice we propose to: (1) Determine the host genetic factors that may influence maternal transmission, virus expression and tumor incidence; (2) to use single gene mutations, some of which have an effect on myelopoiesis, to investigate how specific cell subsets interact with exogenous leukemogenic B-ecotropic MuLV in the development of myeloid leukemia; (3) to determine the time of virus infection (pre or postimplantation) of BXH-2 embryos and to derive ecotropic virus free BXH-2 mice for viral transmission and leukemogenesis studies; (4) to construct recombinant proviruses to determine which sequences within the B-ecotropic proviral genome are determinants for efficient embryo transfer of the virus for myeloid leukemia induction.

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National Cancer Institute (NCI)
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Experimental Virology Study Section (EVR)
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Jackson Laboratory
Bar Harbor
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Cho, B C; Shaughnessy Jr, J D; Largaespada, D A et al. (1995) Frequent disruption of the Nf1 gene by a novel murine AIDS virus-related provirus in BXH-2 murine myeloid lymphomas. J Virol 69:7138-46
Bedigian, H G; Shepel, L A; Hoppe, P C (1993) Transplacental transmission of a leukemogenic murine leukemia virus. J Virol 67:6105-9
Sundberg, J P; Hanson, C A; Roop, D R et al. (1991) Myoepitheliomas in inbred laboratory mice. Vet Pathol 28:313-23
Hurbain-Kosmath, I; Berault, A; Noel, N et al. (1990) Gonadotropes in a novel rat pituitary tumor cell line, RC-4B/C. Establishment and partial characterization of the cell line. In Vitro Cell Dev Biol 26:431-40
Sundberg, J P; Burnstein, T; Shultz, L D et al. (1989) Identification of Pneumocystis carinii in immunodeficient mice. Lab Anim Sci 39:213-8
Davidson, W F; Dumont, F J; Bedigian, H G et al. (1986) Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J Immunol 136:4075-84