Structure of endogenous murine leukemia virus DNA in mouse genomes.

Chattopadhyay, Sisir K.; Lander, Marilyn R.; Rands, Elaine; Lowy, Douglas R.

doi:10.1073/pnas.77.10.5774

Cited by 189 publications

(132 citation statements)

References 29 publications

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“…B/W mice are known to produce a host of endogenous viruses. Although one of the parent strains, NZB, is thought to produce only nonecotropic virus, ecotropic MLV that is derived from the NZW strain (36) can be isolated from the B/W mouse (10,37). When injected with anti-CD4 antibody (38) or with CTLA4Ig (39), and thus prevented from succumbing to lupus disease, B/W mice develop B-cell leukemia.…”

Section: Accumulation Of 2-ltr Sequences From Endogenous MLV By Raltementioning

confidence: 99%

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

Beck-Engeser

Eilat²,

Harrer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Raltegravir is a recently, Food and Drug Administration-approved, small-molecule drug that inhibits retroviral integrase, thereby preventing HIV DNA from inserting itself into the human genome. We report here that the activity profile of raltegravir on the replication of murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role. While NZW and BALB/c mice, which do not succumb to autoimmune disease, are not affected by raltegravir, lupus-prone (NZBx-NZW) F 1 mice die of glomerulonephritis more than a month earlier than untreated mice. Raltegravir-treated NZB mice, which share the H-2 haplotype with BALB/c mice, but which are predisposed to autoimmune hemolytic anemia, develop auto-antibodies to their red blood cells >3 months earlier than untreated mice of the same strain. Because nonautoimmune mice are not affected by raltegravir, we consider off-target effects unlikely and attribute the exacerbation of autoimmunity to the inhibition of retroviral integrase.2-LTR circles ͉ hemolytic anemia ͉ lupus disease ͉ muring leukemia virus ͉ Trex1

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Section: Accumulation Of 2-ltr Sequences From Endogenous MLV By Raltementioning

confidence: 99%

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

Beck-Engeser

Eilat²,

Harrer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…(a) The restriction fragment map of the Lvis1 viral insertion site depicting the position and orientation (5' to 3') of the most frequently observed viral insertion in AKXD leukemias. Representative restriction maps of AKV ecotropic and MCF class II retroviruses (Chattopadhyay et al, 1980) are shown at the top of the ®gure. The shaded box below the map depicts the location of probe pL1.…”

Section: Gene Identi®cationmentioning

confidence: 99%

Activation of Hex and mEg5 by retroviral insertion may contribute to mouse B-cell leukemia

Hansen

Justice

1999

Oncogene

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AKXD recombinant inbred mice develop a variety of leukemias and lymphomas due to retrovirally mediated insertional activation of cellular proto-oncogenes. We describe a new retroviral insertion site that is the most frequent genetic alteration in AKXD B-cell leukemias. Multiple genes¯ank the site of viral insertion, but the expression of just two, Hex and mEg5, is signi®cantly upregulated. Hex is a divergent homeobox gene that is transiently expressed in many hematopoietic lineages, suggesting an involvement in cellular dierentiation. mEg5 is a member of the bim-C subfamily of kinesin related proteins that are necessary for spindle formation and stabilization during mitosis. Our data provide the ®rst genetic evidence for the activation of these genes in leukemia, and suggest that unscheduled expression of Hex and mEg5 contributes to the development of B-cell leukemia. In addition, this work highlights the use of genomic approaches for the study of position eect mutations.

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“…For T cell receptor ␤ chain (TCR␤) rearrangements, digestion was with HpaI and the probe was CT␤ (Hedrick et al, 1985). To screen for somatic integrations of ecotropic MuLV, DNAs were digested with EcoRI and occasionally PvuII and probed with the ecotropic-specific probe EcoSp, a 400-bp SmaI fragment (Chattopadhyay et al, 1980). For analysis of MCF MuLV genomes, an MCF-xenoSp probe (referred to as B-E in Chattopadhyay et al, 1982), which detects MCF and xenotropic MuLV sequences, was used.…”

Section: Molecular Studiesmentioning

confidence: 99%

Accelerated Appearance of Multiple B Cell Lymphoma Types in NFS/N Mice Congenic for Ecotropic Murine Leukemia Viruses

Hartley

Chattopadhyay

Lander

et al. 2000

Laboratory Investigation

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SUMMARY:Spontaneous lymphomas occur at high frequency in NFS.V ϩ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS.V ϩ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor ␤ chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS.V ϩ ) or absence (NFS.V Ϫ ) of functional ecotropic MuLV genomes showed that NFS.V Ϫ clonal lymphomas developed at about one-half the rate of those occurring in NFS.V ϩ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS.V ϩ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis. (Lab Invest 2000, 80:159-169).O ne of the earliest mammalian animal models in cancer research was the AKR mouse strain developed by Jacob Furth about 70 years ago. Selective breeding yielded mice with nearly 100% mortality due to thymic lymphoma in 7 to 14 months (Cole and Furth, 1941). AKR and the limited number of other T cell lymphoma-prone mouse strains (C58, HRS, and some AKXD recombinant inbred (RI) lines) (Gilbert et al, 1993;Green et al, 1980;MacDowell and Richter, 1935;Meier et al, 1969;Mucenski et al, 1986Mucenski et al, , 1988 have been intensively studied, yielding a partial molecular understanding of the role of ecotropic and recombinant mink cell focus-inducing (MCF) murine leukemia viruses (MuLV) in pathogenesis of this earlyonset lymphoma (Cloyd et al, 1980;Hartley et al, 1977;Holland et al, 1985; M c Grath and Weissman, 1979;Rowe and Hartley, 1983;Stoye et al, 1991;Thomas et al, 1984). In contrast to those of T cell lineage, spontaneous B cell lymphomas are most commonly seen in aged mice of strains in which T cell lymphoma does not predominate. For example, the incidence of B cell lymphoma of various types may be 30% or more in unmanipulated, aged BALB/c, C57BL (Frith and Wiley, 1981), AKR.Fv-1 b (HaranGhera et al, 1993), CWD (Angel and Bedigian, 1984;Mucenski et al, 1988;Thomas et al, 1989), or certain AKXD RI lines (Gilbert et al, 1993;Mucenski et al, 1986) held for up to 3 years, as well as in thymectomized AKR (Peled and Haran-Ghera, 1985) and Emyc transgenic mice (Adams et al, 1985). In SL/Kh (Shimada e...

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Structure of endogenous murine leukemia virus DNA in mouse genomes.

Abstract: By using molecularly cloned ecotropic AKR murine leukemia virus (MuLV) DNA, a 400 base-pair ecotropic

Cited by 189 publications

References 29 publications

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

Activation of Hex and mEg5 by retroviral insertion may contribute to mouse B-cell leukemia

Accelerated Appearance of Multiple B Cell Lymphoma Types in NFS/N Mice Congenic for Ecotropic Murine Leukemia Viruses

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