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Y Poirier  C Kozak    P Jolicoeur 《Journal of virology》1988,62(11):3985-3992
Abelson murine leukemia virus induces oligoclonal pre-B lymphoma in mice. The expression of the v-abl oncogene in target cells does not appear to be sufficient for tumor induction in several mouse strains, and additional genetic events are thought to be required. We postulated that the helper Moloney murine leukemia virus might induce these events, and its potential role as an insertional mutagen was assessed by the search of a common helper provirus integration site in Abelson murine leukemia virus lymphomas. Molecular cloning of cellular sequences adjacent to Moloney proviruses enabled us to identify a cellular region, designated Ahi-1, which was found occupied by the helper proviruses in 16% of Abelson pre-B-cell lymphomas. All proviruses for which the precise integration site within Ahi-1 could be mapped were found to be in the same orientation. Ahi-1 has been mapped to mouse chromosome 10 and represents a new common proviral integration site. These data suggest that the helper virus contributes to the induction of secondary genetic events which may be important for the development of Abelson murine leukemia virus-induced pre-B-cell lymphoma.  相似文献   

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Summary We have localised a dystrophin-related autosomal gene called DMDL (Duchenne muscular dystrophy-like) to human chromosome 6q24 by in situ hybridisation. Using restriction fragment length polymorphism analysis in two mouse species, we have localised the homologous gene Dmdl in the mouse to chromosome 10 proximal to the Myb oncogene. A neuromuscular disease locus dystrophia muscularis (dy) has previously been assigned to this region of mouse chromosome 10.  相似文献   

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Proto-oncogen Ahi-1 is closely related to a lot of human and mouse diseases. Ahi-1 mutation will lead to leukemia in mice and Joubert syndrome in human beings. We have cloned the full cDNA sequence of Ahi-1 homologous in zebrafish, and RT-PCR results of ZAhi-1 in different tissues reveal that ZAhi-1 expressed highest in the mature gonad. In situ hybridization results of zebrafish gonad show that ZAhi-1 only expressed in the early stages’ gamete cells. RT-PCR analyses of mouse Ahi-1 in different stages of spermatogenesis have been done according to the published Ahi-1 sequence, and the findings reveal that Ahi-1 is expressed in gamete of pachytene stage. It can then be safely concluded that Ahi-1 might take place in the spermatocyte from the early pachytene stage to the late pachytene stage.  相似文献   

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The fit-1 locus was originally identified as a common insertion site for feline leukemia virus (FeLV) in thymic lymphosarcomas induced by FeLV-myc recombinant viruses, suggesting that it harbors a gene that cooperates with Myc in T-cell leukemogenesis. We have previously mapped the fit-1 locus to feline Chromosome (Chr) B2. We have now identified conserved sequences that allow the mapping of the murine homolog using the European Interspecific Backcross (EUCIB). This shows that fit-1 is located on mouse Chr 10, 1cM proximal to Ahi-1, a murine retroviral integration locus that is closely linked to Myb. Moreover, the physical linkage to MYB is maintained in the human genome, as shown by cloning of the human homolog of fit-1 from a Chr 6 cosmid library and a series of overlapping PAC clones. Generation of a contig map around the human homolog of fit-1 reveals that it is approximately 100-kb upstream of MYB. In addition to fit-1 and Ahi-1, two other common insertion sites, Mis-2 and Mml-1, have also been mapped adjacent to Myb on mouse Chr 10. Previous analysis of tumors carrying insertions at fit-1, Mml-1, Mis-2 and Ahi-1 showed no obvious abnormalities in Myb expression. However, the cluster of viral insertion loci in this region suggests either the presence of a closely linked activation target or that subtle effects on Myb have been overlooked. Received: 9 October 1998 / Accepted: 12 January 1999  相似文献   

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Endogenous retroviruses are known to affect expression of cellular genes in the vicinity of their integration sites. The endogenous mouse mammary tumor provirus (Mtv-8) previously has been reported to reside on mouse chromosome 6 near the immunoglobulin kappa chain locus. Using pairs of mouse strains on the BALB/c (Mtv-8 positive) and C58 (Mtv-8 negative) backgrounds which are congenic for chromosome 6 genetic markers, we have confirmed the chromosome assignment of this provirus. Moreover, we have analyzed the N1 progeny of a (B6 × C58) × C58 backcross to determine the segregation of the Mtv-8 provirus with respect to polymorphisms in the Igk-VSer and Igk-J loci. The results with congenic and backcross mice together with results of others suggest that Mtv-8 is located approximately 0.52 cM from several closely linked kappa markers on chromosome 6.  相似文献   

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The murine retrovirus SL3-3 is a potent inducer of T-cell lymphomas when inoculated into susceptible newborn mice. Previously, DNAs from twenty SL3-3-induced tumors were screened by PCR for provirus integration sites. Two out of 20 tumors demonstrated clonal provirus insertion into a common region. This region has now been isolated and characterized. The region, named SL3-3 integration site 1 (Sint1), maps to the distal end of mouse chromosome 11, corresponding to human chromosome 17q25, and may be identical to a mouse mammary tumor virus integration site in a T-cell lymphoma, Pad3. Two overlapping genomic lambda clones spanning about 35 kb were isolated and used as a starting point for a search for genes in the neighborhood of the virus integration sites. A genomic fragment was used as a hybridization probe to isolate a 3-kb cDNA clone, the expression of which was upregulated in one of two tumors harboring a provirus in Sint1. The cDNA clone is predicted to encode a protein which shows 97.0% identity to a human septin-like protein encoded by a gene which has been found as a fusion partner gene of MLL in an acute myeloid leukemia with a t(11;17)(q23;q25). Together these findings raise the possibility that a proto-oncogene belonging to the septin family, and located about 15 kb upstream of the provirus integration sites, is involved in murine leukemia virus-induced T-cell lymphomagenesis.  相似文献   

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The nondefective Moloney murine leukemia virus (MuLV) induces clonal or oligoclonal T-cell tumors in mice or rats. The proviruses of these nondefective MuLVs have been shown to act as insertion mutagens most frequently activating an adjacent cellular gene involved in cell growth control. Mutations by provirus insertions, recognized as common provirus integration sites, have been instrumental in identifying novel cellular genes involved in tumor formation. We have searched for new common provirus integration sites in Moloney MuLV-induced thymomas. Using cellular sequences flanking a provirus cloned from one of these tumors, we found one region, designated Mis-2, which was the target of provirus integration in a low (3%) percentage of these tumors. Mis-2 was mapped on mouse chromosome 10, approximately 160 kbp downstream of myb. The Mis-2 region may contain a novel gene involved in tumor development.  相似文献   

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The Gross passage A murine leukemia virus (MuLV) induced T-cell leukemia of clonal (or oligoclonal) origin in inoculated mice. To study the role of the integrated proviruses in these tumor cells, we cloned several newly integrated proviruses (with their flanking cellular sequences) from a single tumor in procaryotic vectors. With each of the five clones obtained, a probe was prepared from the cellular sequences flanking the provirus. With one such probe (SS8), we screened several Gross passage A MuLV-induced SIM.S mouse tumor DNAs and found that, in 11 of 40 tumors, a provirus was integrated into a common region designated Gin-1. A 26-kilobase-pair sequence of Gin-1 was cloned from two lambda libraries, and a restriction map was derived. All proviruses were integrated as a cluster in the same orientation within a 5-kilobase-pair region of Gin-1, and most of them had a recombinant structure of the mink cell focus-forming virus type. The frequency of Gin-1 occupancy by provirus was much lower in thymoma induced by other strains of MuLV in other mouse strains. Using somatic-cell hybrid DNAs, we mapped Gin-1 on mouse chromosome 19. Gin-1 was not homologous to 16 known oncogenes and was distinct from the other common regions for provirus integration previously described. Therefore, Gin-1 appears to represent a new common provirus integration region. The integration of a provirus within Gin-1 might be an important event leading to T-cell transformation, and the Gin-1 region might harbor sequences which are involved in tumor development.  相似文献   

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We have previously identified a line of transgenic mice, Tg4, in which an hsp68-lacZ hybrid gene has inserted into the dystonia musculorum (dt) locus on chromosome 1. We have confirmed the localization of the Tg4 integration site to the proximal region of mouse chromosome 1 by interspecific backcross analysis. One end of the integration complex has been cloned and we have used single-copy probes from the flanking region to screen a mouse genomic library. Several overlapping lambda phage clones have been isolated and arranged into a contig spanning 75 kb of genomic DNA. Probes from the genomic contig have enabled us to characterize the wildtype and Tg4 loci. We report that the integration of the transgene was accompanied by a deletion of 45 kb of host genomic sequences with no other detectable rearrangement in the Tg4 genome.  相似文献   

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Bone marrow (BM)-derived T-cell progenitors differentiate into CD4 or CD8 single-positive (SP) cells in the thymus. We have previously reported that a single autosomal mutation, thid, causes a defect in the maturation of CD4 SP thymocytes and an abnormality of peripheral helper T cells in the LEC rat. In this study we attempted to identify a gene responsible for the thid mutation. We first performed genetic linkage analysis and mapped the thid locus between Myb and D1Rat392 on Chr 1. In this region we found an approximately 380-kb deletion from intron 3 of the Ptprk gene, which encodes a receptor-like protein tyrosine phosphatase type κ (RPTPκ) to intron 1 of the RGD1560849 predicted gene in the LEC rat genome. Reconstitution with syngenic BM cells transduced Ptprk but not the RGD1560849 predicted gene rescued development of CD4 SP cells in the LEC rat thymus. It is confirmed by this result that the Ptprk gene is responsible for the thid mutation in the LEC rat. Our results further suggest that RPTPκ plays a critical role in the development of CD4 SP cells in the thymus.  相似文献   

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Rabinowicz PD  Grotewold E 《Planta》2000,211(6):887-893
We have developed a new strategy designated SIMF (Systematic Insertional Mutagenesis of Families), to identify DNA insertions in many members of a gene family simultaneously. This method requires only a short amino acid sequence conserved in all members of the family to make a degenerate oligonucleotide, and a sequence from the end of the DNA insertion. The SIMF strategy was successfully applied to the large maize R2R3 Myb family of regulatory genes, and Mutator insertions in several novel Myb genes were identified. Application of this technique to identify insertions in other large gene families could significantly decrease the effort involved in screening at the same time for insertions in all members of groups of genes that share a limited sequence identity. Received: 1 June 2000 / Accepted: 26 June 2000  相似文献   

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Mutagen treatment of mouse P815 tumor cells produces immunogenic mutants that express new transplantation antigens (tum antigens) recognized by cytolytic T cells. The gene encoding tum antigen P91A comprises 12 exons and a mutation located in exon 4 is responsible for the production of a new antigenic peptide. Transfection experiments showed that the expression of the antigen could be transferred not only by the entire gene but also by gene segments comprising only the mutated exon and parts of the surrounding introns. This was observed with subgenic regions that were not cloned in expression vectors. Antigen expression did not require the integration of the transfected gene segment into a resident P91A gene by homologous recombination. It also occurred when the subgenic segment was transfected without the usual selective gene, which comprises an eucaryotic promoter, and also without plasmid sequences, which are known to contain weak promoters. When a stop codon was introduced at the beginning of exon 4, the expression of the antigen was maintained and evidence was obtained that an ATG codon located in this region served as initiation site for the translation of the antigenic peptide. But we have not obtained evidence indicating that antigenic peptides are direct translation products rather than degradation products of entire proteins. Address correspondence and offprint requests to: T. Boon.  相似文献   

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