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  • *Gene Expression Regulation  (2)
  • Diphtheria Toxin/*genetics
  • 1
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    Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-04-28
    Description: A strategy was devised for identifying regions of the mouse genome that are transcriptionally active in a temporally and spatially restricted manner during development. The approach is based on the introduction into embryonic stem cells of two types of lacZ reporter constructs that can be activated by flanking mouse genomic sequences. Embryonic stem cells containing the lacZ constructs were used to produce chimaeric mice. Developmental regulation of lacZ expression occurred at a high frequency. Molecular cloning of the flanking endogenous genes and introduction of these potential insertional mutations into the mouse germ line should provide an efficient means of identifying and mutating novel genes important for the control of mammalian development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gossler, A -- Joyner, A L -- Rossant, J -- Skarnes, W C -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):463-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mount Sinai Hospital Research Institute, Division of Molecular and Developmental Biology, Toronto, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2497519" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chimera ; Cloning, Molecular ; Embryo, Mammalian/*metabolism ; Galactosidases/*genetics ; *Gene Expression Regulation ; Genetic Vectors ; Germ Cells ; Heat-Shock Proteins/genetics ; Male ; Mice ; Promoter Regions, Genetic ; Stem Cells/*metabolism ; Transfection ; Transformation, Genetic ; beta-Galactosidase/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Regulation of a transcription factor network required for differentiation and metabolism (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-07-31
    Description: Hepatocyte nuclear factors (HNFs) are a heterogeneous class of evolutionarily conserved transcription factors that are required for cellular differentiation and metabolism. Mutations in HNF-1alphaand HNF-4alpha genes impair insulin secretion and cause type 2 diabetes. Regulation of HNF-4/HNF-1 expression by HNF-3alpha and HNF-3beta was studied in embryoid bodies in which one or both HNF-3alpha or HNF-3beta alleles were inactivated. HNF-3beta positively regulated the expression of HNF-4alpha/HNF-1alpha and their downstream targets, implicating a role in diabetes. HNF-3beta was also necessary for expression of HNF-3alpha. In contrast, HNF-3alpha acts as a negative regulator of HNF-4alpha/HNF-1alpha demonstrating that HNF-3alpha and HNF-3beta have antagonistic transcriptional regulatory functions in vivo. HNF-3alpha does not appear to act as a classic biochemical repressor but rather exerts its negative effect by competing for HNF-3 binding sites with the more efficient activator HNF-3beta. In addition, the HNF-3alpha/HNF-3beta ratio is modulated by the presence of insulin, providing evidence that the HNF network may have important roles in mediating the action of insulin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Duncan, S A -- Navas, M A -- Dufort, D -- Rossant, J -- Stoffel, M -- New York, N.Y. -- Science. 1998 Jul 31;281(5377):692-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratories of Molecular Cell Biology and Metabolic Diseases, Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9685261" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Cell Differentiation ; Clone Cells ; DNA-Binding Proteins/genetics/*metabolism ; Diabetes Mellitus, Type 2/genetics/metabolism ; Embryonic and Fetal Development ; Endoderm/cytology/*metabolism ; *Gene Expression Regulation ; *Gene Expression Regulation, Developmental ; Gene Targeting ; Glucose/metabolism ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Hepatocyte Nuclear Factor 3-alpha ; Hepatocyte Nuclear Factor 3-beta ; Hepatocyte Nuclear Factor 4 ; Insulin/pharmacology ; Mice ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Phenotype ; Phosphoproteins/genetics ; Stem Cells ; Transcription Factors/genetics/*metabolism ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Genetic ablation: targeted expression of a toxin gene causes microphthalmia in transgenic mice (1987)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1987-12-11
    Description: Lineage-specific regulatory elements can be used to direct expression of a variety of genes to specific tissues in transgenic mice. If the hybrid constructs contain a gene encoding a cytotoxic gene product, then genetic ablation of a specific cell lineage can be achieved. We have generated six transgenic mice by introducing into fertilized eggs the mouse gamma 2-crystallin promoter fused to the coding region of the diphtheria toxin A-chain gene. Three of these mice and all the transgenic offspring analyzed were microphthalmic. The lenses of these mice displayed considerable heterogeneity: some were almost normal morphologically but reduced in size, whereas others were grossly aberrant and deficient in nuclear fiber cells. These studies indicate that programmed ablation of specific cell types can be stably transmitted through the germ line.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breitman, M L -- Clapoff, S -- Rossant, J -- Tsui, L C -- Glode, L M -- Maxwell, I H -- Bernstein, A -- CA 42354/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1987 Dec 11;238(4833):1563-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3685993" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallins/*genetics ; Diphtheria Toxin/*genetics ; Eye/pathology ; *Genes ; Mice ; Mice, Transgenic ; Microphthalmos/*genetics/pathology ; Promoter Regions, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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