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  • 1
    Online Resource
    Online Resource
    Directed expression of an oncogene to Sertoli cells in transgenic mice using mullerian inhibiting substance regulatory sequences.
    The Endocrine Society ; 1992
    In:  Molecular Endocrinology Vol. 6, No. 9 ( 1992-09), p. 1403-1411
    Details
    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
    URL: Article
    DOI: 10.1210/mend.6.9.1331774
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 1992
    detail.hit.zdb_id: 1492112-1
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  • 2
    Online Resource
    Online Resource
    Two 3' sequences direct adult erythroid-specific expression of human beta-globin genes in transgenic mice.
    Proceedings of the National Academy of Sciences ; 1987
    In:  Proceedings of the National Academy of Sciences Vol. 84, No. 20 ( 1987-10), p. 7056-7060
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 84, No. 20 ( 1987-10), p. 7056-7060
    Abstract: Previous experiments have demonstrated that the human beta-globin gene is correctly regulated in transgenic mice. The beta-globin gene is not expressed in yolk sac-derived erythroid cells in early embryonic development but is expressed concomitantly with the adult mouse beta-globin genes in 14- to 16-day fetal liver and adult reticulocytes. In an attempt to localize sequences that direct erythroid-specific expression, fragments of the human beta-globin gene were inserted in the opposite orientation 200 base pairs (bp) upstream of an intact human A gamma marker gene, which is not expressed on its own in mouse fetal liver. In the experiments reported here, two beta-globin 3' sequences activated the marker gene specifically in fetal liver. One sequence is located in a 250-bp Pst I fragment 550-800 bp downstream from the poly(A) site; the other is located near an EcoRI site in the third exon. These two sequences are active individually, and their combined effect is greater than their effects alone. beta-Globin 5' sequences from -815 to -50 were also analyzed for activity in this assay. The 5' sequences did not activate the marker gene when tested alone but did stimulate expression that was already directed to adult erythroid tissue by the two 3' sequences. These results suggest that three separate sequences are involved in human beta-globin gene regulation. The two 3' sequences act as adult erythroid enhancers and the 5' sequence stimulates expression that is already determined to be erythroid specific.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.84.20.7056
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1987
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Introns increase transcriptional efficiency in transgenic mice.
    Proceedings of the National Academy of Sciences ; 1988
    In:  Proceedings of the National Academy of Sciences Vol. 85, No. 3 ( 1988-02), p. 836-840
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 85, No. 3 ( 1988-02), p. 836-840
    Abstract: Experiments were designed to test the effect of introns on gene expression in transgenic mice. Four different pairs of gene constructs, which were identical except that one member of each pair lacked all introns, were compared for expression of mRNA after introduction into the murine germ line by microinjection of fertilized eggs. The expression of two chimeric genes, made by fusing either the mouse metallothionein I or the rat elastase 1 promoter/enhancer to the rat growth hormone gene, was assayed in fetal liver or pancreas, respectively, while two natural genes, an oligonucleotide-marked mouse metallothionein I gene and the human beta-globin gene, were assayed in fetal liver. In each case there was, on average, 10- to 100-fold more mRNA produced from the intron-containing construct. Moreover, mRNA levels were proportional to the relative rates of transcription that were measured in isolated nuclei. However, when the expression of the two mouse metallothionein I gene-based constructs was tested after transfection into cultured cells, little difference was observed. These observations suggest that introns play a role in facilitating transcription of microinjected genes and that this effect may be manifest only on genes exposed to developmental influences.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.85.3.836
    RVK:
    TA 1000
    RVK:
    WA 15000
    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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  • 4
    Online Resource
    Online Resource
    Protamine 3'-untranslated sequences regulate temporal translational control and subcellular localization of growth hormone in spermatids of transgenic mice.
    Cold Spring Harbor Laboratory ; 1989
    In:  Genes & Development Vol. 3, No. 6 ( 1989-06), p. 793-802
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 3, No. 6 ( 1989-06), p. 793-802
    Abstract: Although the mouse protamine 1 gene (mP1) is first transcribed in round spermatids, its mRNA is not translated until about 1 week later in elongating spermatids. To determine what mP1 sequences are important for its transcriptional and translational regulation, we have constructed fusions between mP1 and the human growth hormone (hGH) structural gene and analyzed their expression in transgenic mice. We show that mP1 sequences 5' to the start of transcription are sufficient to confer spermatid-specific expression on the hGH gene. We also show that 156 nucleotides of mP1 3'-untranslated sequence is sufficient to confer mP1-like translational regulation on the hGH mRNA. Interestingly, the subcellular localization of hGH was dependent on the time during spermiogenesis that it was made. Synthesis of hGH in early round spermatids resulted in localization in the acrosome, whereas synthesis in late elongating spermatids resulted in intracellular, but not acrosomal, localization.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477 , 0890-9369
    URL: Article
    DOI: 10.1101/gad.3.6.793
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1989
    detail.hit.zdb_id: 1467414-2
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice.
    Proceedings of the National Academy of Sciences ; 1991
    In:  Proceedings of the National Academy of Sciences Vol. 88, No. 5 ( 1991-03), p. 1626-1630
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 88, No. 5 ( 1991-03), p. 1626-1630
    Abstract: The human beta-globin locus control region (LCR) is essential for high-level expression of human epsilon-, gamma-, and beta-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human beta-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human beta-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletions of both 5' and 3' sequences, a 373-base-pair (bp) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 18-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.88.5.1626
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1991
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Heart and bone tumors in transgenic mice.
    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
    Details
    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
    URL: Article
    DOI: 10.1073/pnas.85.8.2648
    RVK:
    TA 1000
    RVK:
    WA 15000
    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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  • 7
    Online Resource
    Online Resource
    Genetic analysis of the Müllerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation.
    Cold Spring Harbor Laboratory ; 1996
    In:  Genes & Development Vol. 10, No. 20 ( 1996-10-15), p. 2577-2587
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 10, No. 20 ( 1996-10-15), p. 2577-2587
    Abstract: Müllerian-inhibiting substance (MIS) is a member of the transforming growth factor-beta (TGF-beta) gene family. MIS expression in males causes the regression of the Müllerian ducts, an essential process in male sexual differentiation. Recently, an MIS type II receptor gene has been isolated that is expressed during embryogenesis in mesenchymal cells adjacent to the Müllerian duct epithelium and in Sertoli and granulosa cells of the fetal and adult, male and female gonads, respectively. MIS receptor mutant males develop as internal pseudohermaphrodites, possessing a complete male reproductive tract and also a uterus and oviducts, a phenocopy of MIS ligand-deficient male mice. They express both MIS mRNA and protein, showing that ligand was present, but target organs were hormone-insensitive. All produce sperm, but the majority were infertile because the presence of their female reproductive organs blocks sperm transfer into females. Focal seminiferous tubule atrophy accompanied by Leydig cell hyperplasia was observed and began as early as 2 months of age. The phenotype of MIS ligand/MIS receptor double mutant males was indistinguishable from those of each single mutant. MIS receptor/alpha-inhibin double mutant males developed testicular stromal tumors and large fluid-filled uteri that were identical in phenotype to MIS ligand/alpha-inhibin double mutant males. These studies provide in vivo evidence that MIS is the only ligand of the MIS type II receptor, in contrast to the complexity of other TGF-beta gene family signaling pathways.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.10.20.2577
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1996
    detail.hit.zdb_id: 1467414-2
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Human gamma- to beta-globin gene switching in transgenic mice.
    Cold Spring Harbor Laboratory ; 1990
    In:  Genes & Development Vol. 4, No. 3 ( 1990-03), p. 380-389
    Details
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 4, No. 3 ( 1990-03), p. 380-389
    Abstract: Previous studies demonstrated correct tissue- and temporal-specific expression of human gamma- and beta-globin genes in transgenic mice; however, expression was extremely low. When the erythroid-specific DNase I super-hypersensitive (HS) sites that are normally located upstream of the human beta-globin locus were fused individually to gamma- or beta-globin genes, expression increased to endogenous mouse globin levels but temporal specificity was lost. In contrast, when the HS sequences were combined with fragments containing both gamma- and beta-globin genes, correct developmental regulation was restored. We suggest that human gamma- to beta-globin gene switching during development results from competition of individual globin gene family members for interaction with the HS sequences and that factors influencing these competitive interactions determine temporal specificity.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    URL: Article
    DOI: 10.1101/gad.4.3.380
    RVK:
    WA 15000
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 1990
    detail.hit.zdb_id: 1467414-2
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Transferrin- and albumin-directed expression of growth-related peptides in transgenic sheep
    Oxford University Press (OUP) ; 1991
    In:  Journal of Animal Science Vol. 69, No. 7 ( 1991-07-01), p. 2995-3004
    Details
    In: Journal of Animal Science, Oxford University Press (OUP), Vol. 69, No. 7 ( 1991-07-01), p. 2995-3004
    Type of Medium: Online Resource
    ISSN: 0021-8812 , 1525-3163
    URL: Article
    DOI: 10.2527/1991.6972995x
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1991
    detail.hit.zdb_id: 1490550-4
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Spermatid-specific expression of protamine 1 in transgenic mice.
    Proceedings of the National Academy of Sciences ; 1987
    In:  Proceedings of the National Academy of Sciences Vol. 84, No. 15 ( 1987-08), p. 5316-5319
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 84, No. 15 ( 1987-08), p. 5316-5319
    Abstract: Protamines are abundant basic proteins involved in the condensation of sperm chromatin. In the mouse, protamine genes are transcribed postmeiotically in round spermatids. We have cloned and sequenced the mouse protamine 1 gene. Ten lines of transgenic mice harboring marked protamine 1 sequences were generated by microinjection of fertilized eggs. Transcription of the transgene is restricted to round spermatids and in several cases exceeds that of the endogenous gene. The cis-acting sequences required for tissue-specific protamine expression reside on a 2.4-kilobase restriction fragment. Prospects for using transgenic mice to address fundamental questions of male germ-cell development are discussed.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.84.15.5316
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1987
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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