(16,17). To gain further insights into the pathogenesis of FALS, the studies described in this paper were designed to characterize alterations in the neuronal cytoskeleton in the G1H mice and to compare these alterations with those seen in human ALS.MATERIALS AND METHODS Generation of Human SOD1 Transgenic Mice. The G1H line of transgenic mice carry a human SOD1 gene with a Gly-93 -> Ala substitution (G93A). These derive from a described Gl line (13) and have a 40% expansion in transgene copy number (P. Zhai and M.E.G., unpublished data). The G1H mice have been deposited with the Induced Mutant Resource maintained by The Jackson Laboratory (Bar Harbor, ME) under the strain designation C57BL/6J-TgN(SOD1-G93A)lGur. The N1029
In this study, we have demonstrated the conformational changes to DNA induced by abnormal interactions of copper using circular dichroism, in combination with UV-absorbance and fluorescence spectroscopy. Results confirm that binding of copper to bases of DNA in chromatin is concentration dependent. Binding efficiency of Cu2+ ions to DNA is increased in proportion to the degree of unwinding of the double helix induced by denaturation. Altered B-DNA conformation will alter the integrity of DNA which may affect the normal process of DNA replication and transcription. Copper induced DNA damage in the brain may cause neurotoxicity and the neuronal cell death and is implicated in Alzheimer's disease and other neurological disorders.
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