Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus.
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.
Sørensen
Karina Dalsgaard
KD
Department of Molecular Biology, University of Aarhus, C.F. Møllers Allé, Building 130, DK-8000 Aarhus C, Denmark.
Sørensen
Annette Balle
AB
Quintanilla-Martinez
Leticia
L
Kunder
Sandra
S
Schmidt
Jörg
J
Pedersen
Finn Skou
FS
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009052:Leukemia Virus, Murine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D041681:NIH 3T3 Cells; D010022:Osteopetrosis / Q000473:pathology* / Q000821:virology; D010954:Plasmacytoma / Q000473:pathology* / Q000821:virology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D051839:NFI Transcription Factors; D014157:Transcription Factors