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1.
Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation 总被引：88，自引：0，他引：88
A mouse-human somatic cell hybrid clone, deficient in hypoxanthine-guanine phosphoribosyltransferase (HPRT) and containing a structurally normal inactive human X chromosome, was isolated. The hybrid cells were treated with 5-azacytidine and tested for the reactivation and expression of human X-linked genes. The frequency of HPRT-positives clones after 5-azacytidine treatment was 1000-fold greater than that observed in untreated hybrid cells. Fourteen independent HPRT-positive clones were isolated and analyzed for the expression of human X markers. Isoelectric focusing showed that the HPRT expressed in these clones is human. One of the 14 clones expressed human glucose-6-phosphate dehydrogenase and another expressed human phosphoglycerate kinase. Since 5-azacytidine treatment results in hypomethylation of DNA, DNA methylation may be a mechanism of human X chromosome inactivation. 相似文献
2.
Human thymidine kinase gene locus: assignment to chromosome 17 in a hybrid of man and mouse cells 总被引：9，自引：0，他引：9
O J Miller P W Allderdice D A Miller W R Breg B R Migeon 《Science (New York, N.Y.)》1971,173(993):244-245
The human chromosome retained in a hybrid clone derived from human cells and a moluse line deficiemt in thymidine kinase has the quinacrinefluorescence pattern characteristic of chromosome 17. 相似文献
3.
B F Deys K H Grzeschick A Grzeschick E R Jaffé M Siniscalco 《Science (New York, N.Y.)》1972,175(25):1002-1003
The fibroblasts derived from the skin of a woman heterozygous for an X-linked deficiency of phosphoglycerate kinase represented a mosaic. Two of 22 clones with normal glucose-6-phosphate dehydrogenase activity and hypoxanthine(guanine) phosphoribosyltransferase activity had no phosphoglycerate kinase activity detected by electrophoresis. Because the loci for glucose-6-phosphate dehydrogeniase and hypoxanthine(guanine)phosphoribosyltransferase are already known to undergo inactivation and to be on the short arm of the X chromosome and the locus for phosphoglycerate kinase is on the long arm, these observations support the conclusion that the entire human X chromosome can be involved in X inactivation. 相似文献
4.
Hybridization of Burkitt lymphoblastoid cells 总被引：13，自引：0，他引：13
Burkitt lymphoblastoid cell lines have been fused to mouse and human cell lines with the use of inactivated Sendai virus. The heterokaryons have developed into somatic cell hybrids of both parental cell types. Chromosome analyses confirm that cells now growing in selective medium are hybrids. Initial observations of preparations of the hybrid cells reveal that 5'-iododeoxyuridine can induce continued synthesis of Epstein-Barr virus antigens by these hybrid cells. 相似文献
5.
Chromosomal localization of the human homolog (c-sis) of the simian sarcoma virus onc gene 总被引：34，自引：0，他引：34
Nonrandom chromosome rearrangements of chromosome 22 have been identified in different human malignancies. As a result of Southern blot hybridization of a c-sis probe to DNA's from mouse-human somatic cell hybrids, the human homolog (c-sis) of the transforming gene of simian sarcoma virus was assigned to chromosome 22. Hybrids between thymidine kinase-deficient mouse cells and human fibroblasts carrying a translocation of the region q11-qter of chromosome 22 to chromosome 17 were also analyzed. These studies demonstrate that the human c-sis gene is on region 22q11 greater than qter. 相似文献
6.
The control of cellular senescence by specific human chromosomes was examined in interspecies cell hybrids between diploid human fibroblasts and an immortal, Syrian hamster cell line. Most such hybrids exhibited a limited life span comparable to that of the human fibroblasts, indicating that cellular senescence is dominant in these hybrids. Karyotypic analyses of the hybrid clones that did not senesce revealed that all these clones had lost both copies of human chromosome 1, whereas all other human chromosomes were observed in at least some of the immortal hybrids. The application of selective pressure for retention of human chromosome 1 to the cell hybrids resulted in an increased percentage of hybrids that senesced. Further, the introduction of a single copy of human chromosome 1 to the hamster cells by microcell fusion caused typical signs of cellular senescence. Transfer of chromosome 11 had no effect on the growth of the cells. These findings indicate that human chromosome 1 may participate in the control of cellular senescence and further support a genetic basis for cellular senescence. 相似文献
7.
Repression of rearranged mu gene and translocated c-myc in mouse 3T3 cells X Burkitt lymphoma cell hybrids 总被引：18，自引：0，他引：18
K Nishikura A ar-Rushdi J Erikson E DeJesus D Dugan C M Croce 《Science (New York, N.Y.)》1984,224(4647):399-402
8.
Two lymphocytoid cell lines have been established from a patient with the Lesch-Nyhan syndrome. The cells are deficient in hypoxanthine-guanine phosphoribosyltransferase, as demonstrated by their failure to incorporate [H(3)]hypoxanthine and by their inability to grow in medium in which they were nutritionally dependent upon exogenous hypoxanthine. This represents the first establishment of presumptively permanent human lymphocytoid cell lines that are deficient in a specific enzyme. 相似文献
9.
Somatic cell hybrid between the established human line D98 (presumptive HeLa) and 3T3 总被引：15，自引：0，他引：15
Somatic cell hybrids have been made between an established human cell line with a long culture history and established mouse fibroblast line. When first analyzed, the hybrid cells contained nearly twice as many mouse chromosomes as the mouse parent line and a human chromosome complemnent of about half that of the human parent. There was further loss of human chromosomes on continued cultivation. This behavior resembles that of other human mouse hybrids and appears to be characteristic of the human-mouse combination. However, the number of human chromosomes is greater than in hybrids made from human diploid fibroblasts. Some clones contain more than a haptoid quantity of human DNA per cell and should synthesize a much greater number of human gene products. 相似文献
10.
Cultures of human cells nonpermissive for mouse leukemia virus replication could not be induced to support virus replication by homologous fusion in the presence of Moloney leukemia virus. Human cells were also fused with permissive mouse cells, and the fate of the virus in heterokaryons was determined by a simultaneous autoradiography and fluorescent antibody technique. Heterokaryons containing the full chromosome complement of both cells were likewise nonpermissive for virus synthesis, but hybrids of human and mouse cells, which lacked up to half of the human chromosome complement, were permissive for virus synthesis. The results suggest that human cell genes can direct a repressive control over mouse leukemia virus replication. 相似文献
11.
Expression of a retrovirus encoding human HPRT in mice 总被引：32，自引：0，他引：32
A D Miller R J Eckner D J Jolly T Friedmann I M Verma 《Science (New York, N.Y.)》1984,225(4662):630-632
Transmissible retroviruses encoding human hypoxanthine phosphoribosyltransferase (HPRT) were used to infect mouse bone marrow cells in vitro, and the infected cells were transplanted into mice. Both active human HPRT-protein and chronic HPRT-virus production were detected in hematopoietic tissue of the mice, showing transfer of the gene. These results indicate the possible use of retroviruses for somatic cell therapy. 相似文献
12.
Retroviral vector-mediated gene transfer into human hematopoietic progenitor cells 总被引：13，自引：0，他引：13
H E Gruber K D Finley R M Hershberg S S Katzman P K Laikind J E Seegmiller T Friedmann J K Yee D J Jolly 《Science (New York, N.Y.)》1985,230(4729):1057-1061
The transfer of the human gene for hypoxanthine phosphoribosyltransferase (HPRT) into human bone marrow cells was accomplished by use of a retroviral vector. The cells were infected in vitro with a replication-incompetent murine retroviral vector that carried and expressed a mutant HPRT complementary DNA. The infected cells were superinfected with a helper virus and maintained in long-term culture. The production of progeny HPRT virus by the bone marrow cells was demonstrated with a colony formation assay on cultured HPRT-deficient, ouabain-resistant murine fibroblasts. Hematopoietic progenitor cells able to form colonies of granulocytes or macrophages (or both) in semisolid medium in the presence of colony stimulating factor were present in the nonadherent cell population. Colony forming units cloned in agar and subsequently cultured in liquid medium produced progeny HPRT virus, indicating infection of this class of hematopoietic progenitor cell. 相似文献
13.
Positive control of transformed phenotype in hybrids between SV40-transformed and normal human cells 总被引：5，自引：0，他引：5
Somatic cell hybrids have been obtained between SV40-transformed Lesch-Nyhan fibroblasts, which are deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and display glucose-6-phosphate dehydrogenase A (G6PD-A) activity, and late-passage HGPRT-positive W138 human embryo fibroblasts, which display G6PD-B activity. The human-human hybrid clones, which display G6PD-A and G6PD-B and heteropolymers of the two enzyme forms, have the same growth characteristic as the SV40-transformed parental cells and behave as continuous cell lines. The SV40 tumor antigen, the gene for which has been assigned to human chromosome 7, is present in all clones examined. 相似文献
14.
Gene therapy for human genetic disease? 总被引：16，自引：0，他引：16
In our view, gene therapy may ameliorate some human genetic diseases in the future. For this reason, we believe that research directed at the development of techniques for gene therapy should continue. For the foreseeable future, however, we oppose any further attempts at gene therapy in human patients because (i) our understanding of such basic processes as gene regulation and genetic recombination in human cells is inadequate; (ii) our understanding of the details of the relation between the molecular defect and the disease state is rudimentary for essentially all genetic diseases; and (iii) we have no information on the short-range and long-term side effects of gene therapy. We therefore propose that a sustained effort be made to formulate a complete set of ethicoscientific criteria to guide the development and clinical application of gene therapy techniques. Such an endeavor could go a long way toward ensuring that gene therapy is used in humans only in those instances where it will prove beneficial, and toward preventing its misuse through premature application. Two recent papers have provided new demonstrations of directed genetic modification of mammalian cells. Munyon et al. (44) restored the ability to synthesize the enzyme thymidine kinase to thymidine kinase-deficient mouse cells by infection with ultraviolet-irradiated herpes simplex virus. In their experiments the DNA from herpes simplex virus, which contains a gene coding for thymidine kinase, may have formed a hereditable association with the mouse cells. Merril et al. (45) reported that treatment of fibroblasts from patients with galactosemia with exogenous DNA caused increased activity of a missing enzyme, alpha-D-galactose-l-phosphate uridyltransferase. They also provided some evidence that the change persisted after subculturing the treated cells. If this latter report can be confirmed, the feasibility of directed genetic modification of human cells would be clearly demonstrated, considerably enhancing the technical prospects for gene therapy. 相似文献
15.
Ishikawa K Takenaga K Akimoto M Koshikawa N Yamaguchi A Imanishi H Nakada K Honma Y Hayashi J 《Science (New York, N.Y.)》2008,320(5876):661-664
Mutations in mitochondrial DNA (mtDNA) occur at high frequency in human tumors, but whether these mutations alter tumor cell behavior has been unclear. We used cytoplasmic hybrid (cybrid) technology to replace the endogenous mtDNA in a mouse tumor cell line that was poorly metastatic with mtDNA from a cell line that was highly metastatic, and vice versa. Using assays of metastasis in mice, we found that the recipient tumor cells acquired the metastatic potential of the transferred mtDNA. The mtDNA conferring high metastatic potential contained G13997A and 13885insC mutations in the gene encoding NADH (reduced form of nicotinamide adenine dinucleotide) dehydrogenase subunit 6 (ND6). These mutations produced a deficiency in respiratory complex I activity and were associated with overproduction of reactive oxygen species (ROS). Pretreatment of the highly metastatic tumor cells with ROS scavengers suppressed their metastatic potential in mice. These results indicate that mtDNA mutations can contribute to tumor progression by enhancing the metastatic potential of tumor cells. 相似文献
16.
During cell division, copies of mouse chromosome 7 are segregated selectively or randomly to daughter cells depending on the cell type. The mechanism for differential segregation is unknown. Because mouse left-right dynein (LRD) gene mutations result in randomization of visceral organs' laterality, we hypothesized that LRD may also function in selective chromatid segregation. Indeed, upon knock-down by RNA interference methods, LRD depletion disrupts biased segregation. LRD messenger RNA presence or absence correlates with the observed segregation patterns. This work supports the claim that LRD functions in a mechanism for selective chromatid segregation. 相似文献
17.
Identification of DNA sequence responsible for 5-bromodeoxyuridine-induced gene amplification 总被引：1，自引：0，他引：1
Bromodeoxyuridine (BrdUrd) treatment of the prolactin nonproducing subclone of GH cells (rat pituitary tumor cells) induces amplification of a 20-kilobase DNA fragment including all of the prolactin gene coding sequences. This amplified DNA segment, which is flanked by two unamplified regions, thus designates a unit of BrdUrd-induced amplified sequence. Cloned DNA segments, 10.3 kilobases long, from the 5' end of the rat prolactin gene of BrdUrd-responsive and -nonresponsive cells, were ligated to the thymidine kinase gene of herpes simplex virus type 1 (HSV1TK), and the hybrid DNA was transferred to thymidine kinase-deficient mouse fibroblast cells by transfection. The HSV1TK gene and the rat prolactin gene were amplified together in drug-treated transfectants carrying the hybrid DNA HSV1TK gene and rat prolactin gene of BrdUrd-responsive GH cells. These results suggest that the 10.3-kilobase DNA segment at the 5' end of the rat prolactin gene of BrdUrd-responsive GH cells carries the information for drug-induced gene amplification (amplicon) and that another gene, such as the HSV1TK gene, is also amplified when the latter is placed adjacent to this segment. 相似文献
18.
F A McMorris T R Chen F Ricciuti J Tischfield R Creagan F Ruddle 《Science (New York, N.Y.)》1973,179(78):1129-1131
Thirty-seven clones of somatic cell hybrids between human and mouse cells were examined for retention of human chromosomes and expression of human constitutive enzymes. Human glucosephosphate isomerase and chromosome F-19 were retained or lost concordantly, as were human mannosephosphate isomerase and chromosome C-7. The genes for the enzymes are thus assigned to these two chromosomes. 相似文献
19.
Assignment of the murine interferon sensitivity and cytoplasmic superoxide dismutase genes to chromosome 16 总被引：5，自引：0，他引：5
Both hybrids of mouse and human microcells and whole cell hybrids generated by the fusion of primary mouse cells and SV40-transformed human fibroblasts were used to establish the syntenic association of the murine cytoplasmic superoxide dismutase and the interferon sensitivity genes on mouse chromosome 16. This assignment adds two new markers to chromosome 16 and provides another example of an evolutionarily conserved linkage. This finding also provides an animal model both for cellular responsiveness to interferon and for Down's syndrome. 相似文献
20.
Gene for T-cell growth factor: location on human chromosome 4q and feline chromosome B1 总被引：8，自引：0，他引：8
L J Seigel M E Harper F Wong-Staal R C Gallo W G Nash S J O'Brien 《Science (New York, N.Y.)》1984,223(4632):175-178
T-cell growth factor (TCGF) or interleukin-2 (IL-2), an immunoregulatory lymphokine, is produced by lectin- or antigen-activated mature T lymphocytes and in a constitutive manner by certain T-cell lymphoma cell lines. By means of a molecular clone of human TCGF and DNA extracted from a panel of somatic cell hybrids (rodent cells X normal human lymphocytes), the TCGF structural gene was identified on human chromosome 4. In situ hybridization of the TCGF clone to human chromosomes resulted in significant labeling of the midportion of the long arm of chromosome 4, indicating that the TCGF gene was located at band q26-28. Genomic DNA from a panel of hybrids prepared with HUT-102 B2 cells was examined with the same molecular clone. In this clone of cells, which produces human T-cell leukemia virus, the TCGF gene was also located on chromosome 4 and was apparently not rearranged. The homologous TCGF locus in the domestic cat was assigned to chromosome B1 by using a somatic cell hybrid panel that segregates cat chromosomes. Linkage studies as well as high-resolution G-trypsin banding indicate that this feline chromosome is partially homologous to human chromosome 4. 相似文献