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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Mammalian genome 7 (1996), S. 114-116 
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The locus Om (ovum mutant) identified in the mouse strain DDK affects the viability of (DDK |m~ non-DDK)F1 preimplantation embryos. We previously located this locus on Chromosome (Chr) 11 close to Scya2 (Baldacci et al. Mamm. Genome 2, 100–105, 1992). Here we report a high-resolution map of the region around Om based on a large number of backcross individuals. The same region has been analyzed on the EUCIB backcross, and the two maps have been compared. The results define the proximal and distal boundaries for the Om mutation as Scya2 and D11Mit36 respectively. The distance between these two markers is about 2 cM. These data should facilitate the positional cloning and molecular characterization of Om.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Tay-Sachs disease is an autosomal recessive lysosomal storage disease caused by β-hexosaminidase A deficiency and leads to death in early childhood. The disease results from mutations in the HEXA gene, which codes for the α chain of β-hexosaminidase. The catastrophic neurodegenerative progression of the disease is thought to be a consequence of massive neuronal accumulation of GM2 ganglioside and related glycolipids in the brain and nervous system of the patients. Fuller understanding of the pathogenesis and the development of therapeutic procedures have both suffered from the lack of an animal model. We have used gene targeting in embryonic stem (ES) cells to disrupt the mouse Hexa gene. Mice homozygous for the disrupted allele mimic several biochemical and histological features of human Tay-Sachs disease. Hexa-/-mice displayed a total deficiency of β-hexosaminidase A activity, and membranous cytoplasmic inclusions typical of GM2 gangliosidoses were found in the cytoplasm of their neurons. However, while the number of storage neurons increased with age, it remained low compared with that found in human, and no apparent motor or behavioral disorders could be observed. This suggests that the presence of β-hexosaminidase A is not an absolute requirement of ganglioside degradation in mice. These mice should help us to understand several aspects of the disease as well as the physiological functions of hexosaminidase in mice. They should also provide a valuable animal model in which to test new forms of therapy, and in particular gene delivery into the central nervous system.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1058-8388
    Keywords: Embryonic development ; MHC gene regulation ; Transgenic mice ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The pattern of expression of the H-2K major histocompatibility complex (MHC) class I gene is complex. During embryonic development H-2K mRNA, detectable from midgestation, is poorly expressed. In the adult, H-2K expression is nearly ubiquitous but transcriptional regulation occurs leading to different mRNA levels in the different organs of the mouse. In vitro studies have shown that most of the regulatory elements controlling H-2K gene transcription are located in the 5′ region of the gene. However, using fusion transgenes in which reporter genes were under the control of 2 kb of H-2K 5′ regulatory region, we have previously shown that this region, was not sufficient to ensure correct developmental transgene expression. By contrast, a native 9.25 kb H-2K transgene was expressed appropriately both in the adult and in the embryo. In order to localise more precisely the cis-acting regulatory sequences involved in H-2K developmental expression, we have now constructed new transgenic lines containing H-2Kb transgenes that were deleted from specific parts of the H-2Kb gene. We show that deletion of either the H-2K 3′ flanking region or the 5 (out of 7) distal introns results in an expression of the transgenes which is similar to that of the endogenous H-2K gene, both in the adult and during embryonic development. By contrast, deletion of all the introns or of the two proximal ones abrogates H-2K transgene expression. Our data reveal the complexity of H-2K regulation and highlight the crucial role of proximal introns in H-2K expression in the living organism. © 1995 wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 33 (1992), S. 149-159 
    ISSN: 1040-452X
    Keywords: Development ; Fusion genes ; β-Galactosidase ; Position effect ; Transgenic mice ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: In order to study sequences in volved in the developmentally regulated and tissue-specific expression of the class I Major Histocompatibility Complex (MHC) genes, we have constructed several H-2/lacZ transgenic lines in which the 5′ regulatory sequences of the H-2Kb gene are linked to the Escherichia coli β-galactosidase (lacZ) gene. In five H-2/lacZ lines, the pattern of lacZ expression, detected histochemically varied greatly from line to line. None of the H-2/lacZ transgenes were transcribed in cells normally expressing a high level of endogenous H-2 molecules, although these H-2 regulatory sequences have been shown to be sufficient to drive tissuespecific expression of other reporter genes. Interstingly, when constructs containing 5′ β2-microglobulin (β2m) regulatory sequences linked to lacZ were used to derive transgenic lines, similar results were obtained. A survey of lacZ labeling in H-2/lacZ and β2m/lacZ transgenic mice strongly suggests that these transgenes are very sensitive to position effect, lacZ expression being controlled by endogenous chromosomal regulatory elements specific for each insertion site. Here we describe the complex pattern of lacZ expression in the different transgenic lines during development; we discuss the unusual properties of these transgenes and underline their potential use for developmental studies and characterization of genomic sequences involved in spatiotemporal gene expression. © 1992 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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