Studies from University of California, Cancer Center in the area of Cockayne syndrome published
2007 FEB 26 -- New research, "Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in repair-deficient Cockayne syndrome mice," is the subject of a report. "Cockayne syndrome (CS) is a rare recessive childhood-onset neurodegenerative disease, characterized by a deficiency in the DNA repair pathway of transcription-coupled nucleotide excision repair. Mice with a targeted deletion of the CSB gene (Csb-/-) exhibit a much milder ataxic phenotype than human patients," scientists in the United States report. "Csb-/-mice that are also deficient in global genomic repair [Csb-/-/xeroderma pigmentosum C (Xpc)-/-] are more profoundly affected, exhibiting whole-body wasting, ataxia, and neural loss by postnatal day 21. Cerebellar granule cells demonstrated high TUNEL staining indicative of apoptosis. Purkinje cells, identified by the marker calbindin, were severely depleted and, although not TUNEL-positive, displayed strong immunoreactivity for p53, indicating cellular stress. A subset of animals heterozygous for Csb and Xpc deficiencies was more mildly affected, demonstrating ataxia and Purkinje cell loss at 3 months of age. Mouse, Csb-/-, and Xpc-/-embryonic fibroblasts each exhibited increased sensitivity to UV light, which generates bulky DNA damage that is a substrate for excision repair. Whereas Csb-/-/Xpc-/-fibroblasts were more UV-sensitive than either single knockout, double-heterozygote fibroblasts had normal UV sensitivity. Csb-/-mice crossed with a strain defective in base excision repair (Ogg1) demonstrated no enhanced neurodegenerative phenotype," wrote R.R. Laposa and colleagues, University of California, Cancer Center. The researchers concluded: "Complete deficiency in nucleotide excision repair therefore renders the brain profoundly sensitive to neurodegeneration in specific cell types of the cerebellum, possibly because of unrepaired endogenous DNA damage that is a substrate for nucleotide but not base excision repair." Laposa and colleagues published their study in Proceedings of the National Academy of Sciences of the United States of America (Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in repair-deficient Cockayne syndrome mice. Proceedings of the National Academy of Sciences of the United States of America, 2007;104(4):1389-94). For additional information, contact R.R. Laposa, University of California, Dept. of Dermatology and Cancer Center, San Francisco, CA 94143-0808 USA. The publisher's contact information for the journal Proceedings of the National Academy of Sciences of the United States of America is: National Acad Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA. Keywords: United States, San Francisco, Ataxia, Cockayne Syndrome, DNA Damage, DNA Research, Deoxyribonucleic Acid, Mental Health, Neurodegenerative, Neurology, Proteomics. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.
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