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Murine Models

Genetic factors influencing the development of chronic graft-versus-host disease in a murine model

Abstract

Graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation that can occur in either acute or chronic forms. Much of the long-term pathology seen in chronic GVHD is a result of autoantibody production. In the DBA/2 → B6D2F1 murine model of chronic GVHD, anti-ssDNA autoantibodies can be detected by 14 days post cell transfer. These autoantibodies are not observed in B6D2F1 recipients of cells from C57BL/6 or B10.D2 donors, which develop acute rather than chronic GVHD. Therefore, in this model, donor genetic factors predispose to the development of chronic GVHD in recipients. We performed a genetic analysis aimed at mapping donor loci that influence the magnitude of early autoantibody production in B6D2F1 recipients of cells from DBA/2 donor mice. Linkage analysis suggested an influence of two loci: a locus on chromosome 11 linked to D11Mit278 and a locus on chromosome 4 linked to D4Mit226. The locus on chromosome 11 also appeared to influence the development of renal pathology associated with chronic GVHD. Bone Marrow Transplantation (2000) 26, 931–938.

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Acknowledgements

We would like to thank John Allyn, Paul Anderson and Anjana Patel for technical assistance in the laboratory. This work was funded by grant AI 33026 from the National Institutes of Health.

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Slayback, D., Dobkins, J., Harper, J. et al. Genetic factors influencing the development of chronic graft-versus-host disease in a murine model. Bone Marrow Transplant 26, 931–938 (2000). https://doi.org/10.1038/sj.bmt.1702661

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