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Fv2 encodes a truncated form of the Stk receptor tyrosine kinase

Nature Genetics volume 23, pages 159–165 (1999)Cite this article

Abstract

The Friend virus susceptibility 2 (Fv2) locus encodes a dominant host factor that confers susceptibility to Friend virus-induced erythroleukaemia in mice. We mapped Fv2 to a 1.0-Mb interval that also contained the gene (Ron) encoding the stem cell kinase receptor (Stk). A truncated form of Stk (Sf-stk), which was the most abundant form of Stk in Fv2-sensitive (Fv2ss) erythroid cells, was not expressed in Fv2 resistant (Fv2rr) cells. Enforced expression of Sf-stk conferred susceptibility to Friend disease, whereas targeted disruption of Ron caused resistance. We conclude that the Fv2 locus encodes Ron, and that a naturally expressed, truncated form of Stk confers susceptibility to Friend virus-induced erythroleukaemia.

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Figure 1: Fv2 is located between markers Gnat1 and D9Mit184 .
Figure 2: Sf-stk is not expressed in Fv2rr erythroid cells.
Figure 3: Stk-deficient mice are resistant to Friend virus disease.
Figure 4: Acute erythroblastosis in Sf-stk transplanted mice infected with FVP.
Figure 5: Erythroleukaemia in Sf-stk transplanted mice infected with FVP.

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Acknowledgements

We thank A. Troutman and J. Swift for technical support; J. Riberdy and P. Doherty for anti-Cd4 and anti-Cd8 antibody; J. Ihle, M. Bondurant and M. Hayman for reviewing the manuscript; and A. Nienhuis and G. Grosveld for additional support. This work was supported by NIH Cancer Center Support Grant No. P30 CA21765, the American Lebanese Syrian Associated Charities (ALSAC), an American Society of Hematology Junior Faculty Scholarship Award to P.H.C. and a Terry Fox Program Project Grant from the National Cancer Institute of Canada to A.B.

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Author notes

  1. Derek A. Persons and Robert F. Paulson: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, 38105 , Tennessee, USA

    Derek A. Persons

  2. Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, 38105, Tennessee, USA

    Melanie R. Loyd, Mark T. Herley & Paul A. Ney

  3. Department of Pathology, St. Jude Children's Research Hospital, Memphis, 38105, Tennessee, USA

    Sara M. Bodner

  4. Department of Veterinary Science, Pennsylvania State University, University Park, 16802, Pennsylvania, USA

    Robert F. Paulson & Pamela H. Correll

  5. Samuel Lunenfeld Research Institute and Department of Molecular and Medical Genetics, Program in Molecular Biology and Cancer, Mount Sinai Hospital, University of Toronto, Toronto, Ontario , Canada

    Alan Bernstein

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Correspondence to Paul A. Ney.

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Persons, D., Paulson, R., Loyd, M. et al. Fv2 encodes a truncated form of the Stk receptor tyrosine kinase . Nat Genet 23, 159–165 (1999). https://doi.org/10.1038/13787

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