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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Development genes and evolution 208 (1998), S. 128-134 
    ISSN: 1432-041X
    Keywords: Key words Pax-3 ; Licensing factor ; cdc46 ; Neural tube
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  CDC46/MCM5 encodes a protein that is highly conserved among yeast, plants, and animals. It is found in a complex which exhibits DNA replication licensing activity, which is proposed to regulate the synthesis of DNA once and only once per cell cycle. In yeast, loss of function mutations of CDC46/MCM5 decrease DNA synthesis. Very little is known about the regulation of CDC46/MCM5 in any species. We report here that, in the mouse embryo, expression of cdc46 is increased in unfused portions of the neural tube when the gene encoding the transcription factor, Pax-3, is either nonfunctional or underexpressed. These results were observed both in embryos of diabetic mice, which we have previously shown express significantly reduced levels of Pax-3 mRNA, and in Splotch embryos, which carry loss of function Pax-3 alleles. This indicates that expression of cdc46 is negatively regulated as part of a Pax-3-dependent pathway. Since cdc46 appears to regulate DNA synthesis and cell cycle progression, it is possible that its overexpression is involved in defective embryonic development that is associated with loss of Pax-3 function.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glycogen phosphorylase ; muscle ; gene expression ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glycogen phosphorylase regulates the breakdown of glycogen into glucose, but as previous studies have demonstrated, the control of glycogen metabolism becomes deregulated in diabetes mellitus. Messenger RNA levels encoding several different proteins are altered in skeletal muscle biopsies of patients with insulin-dependent and non-insulin-dependent diabetes. The possible alteration of expression of the gene encoding the skeletal muscle isoform of glycogen phosphorylase during diabetes has not previously been investigated. We examined the effect of streptozotocin-induced diabetes and insulin treatment on glycogen phosphorylase mRNA in rat skeletal muscle; glycogen phosphorylase mRNA levels were elevated in diabetic rat muscle tissue, but were partially suppressed in diabetic rat muscle following insulin treatment. To distinguish between the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA levels, we employed differentiating rat L6 myoblasts in culture. Insulin stimulated the accumulation of glycogen phosphorylase mRNA as determined by Northern blot analysis. Moreover, insulin and dibutyryl cAMP stimulated expression of a transiently transfected chloramphenicol acetyl transferase reporter gene under the control of the muscle glycogen phosphorylase promoter in differentiating myotubes in culture, suggesting that the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA are at the level of transcription. These results suggest that insulin and epinephrine may participate in the induction of the glycogen phosphorylase gene during myogenesis; moreover, activation of this gene in muscle tissue may be a contributing factor in impaired glycogen storage during uncontrolled diabetes.
    Type of Medium: Electronic Resource
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