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  • 1
    In: Molecular Endocrinology, The Endocrine Society, Vol. 6, No. 9 ( 1992-09), p. 1403-1411
    Type of Medium: Online Resource
    ISSN: 0888-8809 , 1944-9917
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 1992
    detail.hit.zdb_id: 1492112-1
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  • 2
    Online Resource
    Online Resource
    Informa UK Limited ; 1989
    In:  Molecular and Cellular Biology Vol. 9, No. 11 ( 1989-11), p. 5154-5162
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 9, No. 11 ( 1989-11), p. 5154-5162
    Abstract: Transferrin is an iron-binding protein that is expressed as a major product in liver and secreted into the plasma. To study the tissue-specific regulatory regions of this gene, the genomic mouse transferrin (mTf) gene was cloned and characterized by partial sequence analysis and S1 nuclease mapping of the transcriptional start site. Fusion genes containing the transferrin gene promoter and 5'-flanking sequences were ligated to the human growth hormone (hGH) gene and used to produce transgenic mice. A deletion construct containing the -581 to +50 region of the transferrin gene was sufficient to direct a high level of liver-specific expression resembling endogenous transferrin gene expression. Deletion to -139 base pairs of 5'-flanking sequence gave a construct which retained liver specificity, but the magnitude of expression decreased severalfold. These results demonstrate the presence of a liver-specific transcriptional element between -139 and +50 and suggest the presence of a distal element between -581 and -139 that can further increase expression. Surprisingly, fusion constructs containing -3 kilobase pairs (kb) of 5'-flanking sequence gave higher levels of mRNA in nonhepatic tissues than did either the -581 or -139 construct. Further studies indicated that the high levels of circulating hGH in these transgenic mice specifically induced the endogenous transferrin and albumin genes in liver and also stimulated the normally low levels of expression of the endogenous transferrin gene in brain, heart, kidney, and muscle. A mutated hGH gene that does not produce active growth hormone was fused to the -3- to +50-kb transferrin sequences to produce the -3-kb mTf-hGX construct. A liver-specific pattern of expression was observed in transgenic mice harboring the -3-kb mTf-hGX construct, and this mutated transgene was shown to be induced four- to sevenfold by either bovine or human growth hormone. These results demonstrate the presence of a growth hormone-responsive element between -3 and +50 kb in the 5'-flanking region of the mTf gene promoter.
    Type of Medium: Online Resource
    ISSN: 0270-7306 , 1098-5549
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1989
    detail.hit.zdb_id: 1474919-1
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Informa UK Limited ; 1986
    In:  Molecular and Cellular Biology Vol. 6, No. 4 ( 1986-04), p. 1010-1014
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 6, No. 4 ( 1986-04), p. 1010-1014
    Abstract: The intact chicken transferrin gene was microinjected into fertilized mouse eggs, and the resulting transgenic animals were used to produce lines of mice containing integrated copies of the chicken gene. The levels of expression of the chicken gene were quantitated in various tissues, and the response of the gene to estrogen stimulation was measured after chronic or acute estrogen exposure. Two of the three mouse lines studied maintained stable levels of expression in successive generations of offspring, and the third line had two- to threefold-higher levels in offspring than in the original parent. In the third line, the original transgenic parent was found to be a mosaic. The chicken transferrin gene was expressed at 10- to 20-fold-higher levels in liver than in any other tissue; however, the levels of chicken transferrin mRNA in kidney were higher than expected, indicating that the tissue specificity was only partial. In all three lines, the foreign gene was induced by estrogen administration. After 10 days of estrogen administration, there was a twofold increase in both transferrin mRNA and transcription of the chicken transferrin gene. A single injection of estradiol led to a fourfold increase in transferrin mRNA synthesis at 4h. As a control the levels of mouse albumin were measured, and both the level of albumin mRNA and its rate of transcription declined about twofold after estrogen administration. Our results indicate that the intact chicken gene with 2.2 kilobases of 5' flanking sequence contains signals for both tissue specificity and steroid regulation that can be recognized in mice.
    Type of Medium: Online Resource
    ISSN: 0270-7306 , 1098-5549
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1986
    detail.hit.zdb_id: 1474919-1
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 1987
    In:  Nature Vol. 326, No. 6111 ( 1987-3), p. 405-409
    In: Nature, Springer Science and Business Media LLC, Vol. 326, No. 6111 ( 1987-3), p. 405-409
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1987
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 1962
    In:  Nature Vol. 194, No. 4830 ( 1962-5), p. 747-749
    In: Nature, Springer Science and Business Media LLC, Vol. 194, No. 4830 ( 1962-5), p. 747-749
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1962
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 1988
    In:  Genes & Development Vol. 2, No. 4 ( 1988-04), p. 453-461
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 2, No. 4 ( 1988-04), p. 453-461
    Abstract: Fusion of the 310 bp located 5' of the rat growth hormone (GH) gene to the human GH structural gene resulted in somatotrope-specific expression in transgenic mice. Human GH transcripts were detected only in pituitaries of these mice, and immunocytochemical analyses revealed that this expression was limited to GH-expressing cell types. The rat GH 5' sequences were then used to direct the expression of diphtheria toxin to the GH-expressing cells of transgenic mice. A line of mice was established which lacks detectable levels of circulating GH. This deficiency resulted in dwarfism; transgenic animals grew only to half the size of nontransgenic littermates. Nearly all somatotropes were absent, as shown by GH immunostaining in the transgenic pituitaries. Prolactin (PRL)-producing lactotropes, thought to share a common cellular origin with somatotropes, were also reduced in numbers. A model for the lineal relationships between GH- and PRL-synthesizing cells is proposed.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1988
    detail.hit.zdb_id: 1467414-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1992
    In:  Proceedings of the National Academy of Sciences Vol. 89, No. 23 ( 1992-12), p. 11523-11527
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 89, No. 23 ( 1992-12), p. 11523-11527
    Abstract: Hepatocyte-directed production of urokinase-type plasminogen activator (uPA) in transgenic mice is hepatotoxic. Infrequently, hepatocytes arise that do not express uPA, due to physical loss of transgene DNA, and these cells clonally repopulate the entire liver within 3 months of birth. Surprisingly, hepatic tumors appear in these mice beginning at 8 months of age despite the fact that uPA is not oncogenic or genotoxic. Analysis of the transgene locus reveals that tumors arise only from a particular subclass of transgene-deficient cells in which the entire transgene array, and possibly a significant amount of flanking DNA, is deleted. Considering that all transgene-deficient regenerative nodules undergo extensive replication but only a subset gives rise to tumors, we propose that loss of genomic DNA, not mitogenesis per se, is a primary carcinogenic determinant in this model of hepatocarcinogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1992
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Informa UK Limited ; 1987
    In:  Molecular and Cellular Biology Vol. 7, No. 10 ( 1987-10), p. 3466-3472
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 7, No. 10 ( 1987-10), p. 3466-3472
    Abstract: An elastase-human growth hormone (hGH) fusion gene containing 205 base pairs of elastase 5' flanking region is expressed exclusively in pancreatic acinar cells of transgenic mice. This paper shows that the promoter region (-72 to +8) and the enhancer (-205 to -73) function independently of each other. The elastase enhancer can activate the heterologous mouse metallothionein gene and the hGH gene promoters; conversely, enhancers from the thymocyte-specific murine leukemia virus MCF13 and the metal regulatory elements from the metallothionein gene can activate the elastase promoter in a variety of cell types. Combinations of immunoglobulin and elastase enhancers with a heterologous promoter and the hGH gene result in expression in all of the tissues predicted by the sum of each enhancer acting alone. Thus these enhancer elements act independently of each other, suggesting that they do not have silencing activity in cells in which they are normally inactive.
    Type of Medium: Online Resource
    ISSN: 0270-7306 , 1098-5549
    RVK:
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 1987
    detail.hit.zdb_id: 1474919-1
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1988
    In:  Proceedings of the National Academy of Sciences Vol. 85, No. 8 ( 1988-04), p. 2648-2652
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 85, No. 8 ( 1988-04), p. 2648-2652
    Abstract: Tissue-specific tumorigenesis can be induced in transgenic mice by the directed expression of simian virus 40 (SV40) large tumor (T) antigen. In an attempt to determine the susceptibility of haploid, round spermatids to neoplastic transformation by this oncogene, transgenic mice were generated that harbored a chimeric gene composed of the SV40 T-antigen genes fused to the 5' and 3' flanking sequences of the mouse protamine 1 gene. The transgene was expressed in round spermatids and, surprisingly, in the heart and temporal bone as well. Expression in the heart resulted in rhabdomyosarcomas that always appeared in the right atrium. Bilateral osteosarcomas developed within the petrous portion of the temporal bone. No testicular pathology was observed. T-antigen immunostaining was readily detected in tumor tissue but not in the testis. In addition, SV40 transcripts were processed differently in testis and tumor tissue. Transgenic mouse lines were established that routinely develop these tumors, and they should provide a valuable resource for studies involving cardiac and bone physiology and neoplasia. The atrial tumor cells can be maintained in vitro and some continue to display a cardiac muscle phenotype.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1988
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    The American Association of Immunologists ; 1989
    In:  The Journal of Immunology Vol. 142, No. 6 ( 1989-03-15), p. 2081-2088
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 142, No. 6 ( 1989-03-15), p. 2081-2088
    Abstract: Class II genes of the MHC must be expressed by APC for activation of CD4+ T cells and efficient delivery of T cell help to B lymphocytes. Class II genes have restricted tissue expression and are under complex regulation. By using various deletion constructs of the class II E alpha d gene in transgenic mice we have mapped different 5' flanking regions which control E alpha d gene expression in distinct cell types. We demonstrate dissociate expression of E alpha d within the macrophage lineage as well as within the B cell lineage, and present evidence for a repressive element operative in B cells and macrophages. We describe the generation of novel transgenic lines with limited constitutive and inducible E alpha mRNA and I-E protein.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1989
    detail.hit.zdb_id: 1475085-5
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