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M9620386.TXT
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1996-02-26
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Document 0386
DOCN M9620386
TI Frequent disruption of the Nf1 gene by a novel murine AIDS virus-related
provirus in BXH-2 murine myeloid lymphomas.
DT 9602
AU Cho BC; Shaughnessy JD Jr; Largaespada DA; Bedigian HG; Buchberg AM;
Jenkins NA; Copeland NG; Mammalian Genetics Laboratory, ABL-Basic
Research Program,; NCI-Frederick Cancer Research and Development Center,
Maryland; 21702, USA.
SO J Virol. 1995 Nov;69(11):7138-46. Unique Identifier : AIDSLINE
MED/96013817
AB Evi-2, a common site of viral integration in BXH-2 myeloid lymphomas, is
located within a large intron of the Nf1 tumor suppressor gene. Viral
integration at Evi-2 appears to induce disease by disrupting normal Nf1
expression. During our attempts to characterize the nature of the
proviruses located at Evi-2, we found that approximately half of the
proviruses were defective nonecotropic proviruses (A. M. Buchberg, H. G.
Bedigian, N. A. Jenkins, and N. G. Copeland, Mol. Cell. Biol.
10:4658-4666, 1990). This was surprising, since most proviruses
characterized at other BXH-2 common integration sites are full-length
ecotropic viruses. In the studies described here, we found that this
defective provirus carries two large deletions, one in pol and one in
env, and is structurally related to another murine retrovirus, the
murine AIDS retrovirus. By using oligonucleotide probes specific for
this defective provirus, designated MRV, we showed that MRV-related
proviruses are carried as endogenous germ line proviruses in most inbred
strains. In addition, we identified the endogenous MRV provirus that
gives rise to the defective proviruses identified at Evi-2. We present a
model that accounts for the positive selection of MRV proviruses at
Evi-2, which may allow selective identification of common viral
integration sites harboring tumor suppressor genes.
DE Acquired Immunodeficiency Syndrome/GENETICS Amino Acid Sequence Animal
Base Sequence Blotting, Southern *Chromosome Mapping Comparative
Study DNA Primers DNA, Neoplasm/ANALYSIS/GENETICS DNA,
Viral/ANALYSIS/GENETICS Gene Library Gene Products,
gag/CHEMISTRY/GENETICS *Genes, gag *Genes, Neurofibromatosis 1
Lymphoma/*GENETICS/*VIROLOGY Mice Mice, Inbred Strains Molecular
Sequence Data Murine Acquired Immunodeficiency Syndrome/*VIROLOGY
Oligonucleotide Probes Proviruses/*GENETICS/ISOLATION & PURIF
Repetitive Sequences, Nucleic Acid Retroviridae/*GENETICS/ISOLATION &
PURIF Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support,
U.S. Gov't, P.H.S. JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).