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Digitale Medien

T cells in aging mice: genetic, developmental, and biochemical analyses (2005)

Miller, Richard A. ; Berger, Scott B. ; Burke, David T. ; [weitere]

Oxford, UK; Malden, USA : Munksgaard International Publishers

Immunological reviews 205 (2005), S. 0

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ISSN: 1600-065X

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Summary: A combination of approaches – gene mapping, biomarker analysis, and studies of signal transduction – has helped to clarify the mechanisms of age-related change in mouse immune status and the implications of immune aging for late-life disease. Mapping studies have documented multiple quantitative trait loci (QTL) that influence the levels of age-sensitive T-cell subsets. Some of these QTL have effects that are demonstrable in young-adult mice (8 months of age) and others demonstrable only in middle-aged mice (18 months). Biomarker studies show that T-cell subset levels measured at 8 or 18 months are significant predictors of lifespan for mice dying of lymphoma, fibrosarcoma, mammary adenocarcinoma, or all causes combined. Mice whose immune systems resemble that of young animals, i.e. with low levels of CD4+ and CD8+ memory T cells and relatively high levels of CD4+ T cells, tend to outlive their siblings with the opposite subset pattern. Biochemical analyses show that T cells from aged mice show defects in the activation process within a few minutes of encountering a stimulus and that the defects precede the recognition by the T-cell receptor of agonist peptides on the antigen-presenting cell. Defective assembly of cytoskeletal fibers and hyperglycosylation of T-cell surface glycoproteins contribute to the immunodeficiency state, and indeed treatment with a sialylglycoprotein endopeptidase can restore full function to CD4+ T cells from aged donors in vitro.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1111/j.0105-2896.2005.00254.x

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Digitale Medien

Coordinate control and variation in X-linked gene expression among female mice (1997)

Greenwood, Alex D. ; Southard-Smith, E. Michelle ; Galecki, Andrzej T. ; [weitere]

Springer

Mammalian genome 8 (1997), S. 818-822

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ISSN: 1432-1777

Quelle: Springer Online Journal Archives 1860-2000

Thema: Biologie , Medizin

Notizen: Abstract. In normal female mammals, one of the two X Chromosome (Chr) homologs per cell is silenced coordinately during early embryogenesis. The genes located on the inactivated X homolog are predicted to be influenced by the same underlying repression mechanism. To test the uniformity of cis-acting gene repression, 32 genetically identical F1 female mice were analyzed for differential expression of homologous alleles at three X-linked genes—Otc, Atp7a (=Mottled), and Hprt. Gene expression was assayed by the single-nucleotide primer extension (SNuPE) method, thereby allowing the three genes to be quantitated from the same RNA sample. Although variable between individual animals, the relative expression of the two alleles (allelic expression ratio) of the genes is significantly correlated within each steady-state RNA pool. When examined by animal age (3 months to 12 months), no statistically significant differences were observed in the mean or variance of allelic expression ratio. Together, the results confirm that X inactivation is coordinately controlled and is stable across the early- to mid-adult life span.