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Karina Dalsgaard Sørensen

Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus

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  • Department of Molecular Biology
Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity.
Original languageEnglish
JournalVirology
Volume334
Issue2
Pages (from-to)234-244
Number of pages11
ISSN0042-6822
DOIs
Publication statusPublished - 2005

    Research areas

  • Animals, Base Sequence, Binding Sites, CCAAT-Enhancer-Binding Proteins, Cell Line, Enhancer Elements (Genetics), Gene Expression Regulation, Viral, Humans, Leukemia Virus, Murine, Mice, Molecular Sequence Data, NFI Transcription Factors, NIH 3T3 Cells, Osteopetrosis, Plasmacytoma, Transcription Factors

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