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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease ( HD) transgenic mice and HD patients.

Huntington's disease ( HD) is a progressive neurological disorder caused by a CAG/polyglutamine repeat expansion. We have previously generated the R6/2 mouse model that expresses exon 1 of the human HD gene containing CAG repeats in excess of 150. These mice develop a progressive neurological phenotype with a rapid onset and progression. We show here that it is impossible to establish fibroblast lines from these mice at 12 weeks of age, whilst this can be achieved without difficulty at 6 and 9 weeks. Cultures derived from mice at 12 weeks contained a high frequency of dysmorphic cells, including cells with an aberrant nuclear morphology and a high frequency of micronuclei and large vacuoles. All of these features were also present in a line derived from a juvenile HD patient. Fibroblast lines derived from R6/2 mice and from HD patients were found to have a high frequency of multiple centrosomes which could account for all of the observed phenotypes including a reduced mitotic index, high frequency of aneuploidy and persistence of the midbody. We were unable to detect large insoluble polyglutamine aggregates in either the mouse or human lines. We have identified a novel progressive HD pathology that occurs in cells of non-central nervous system origin. An investigation of the pathological consequences of the HD mutation in these cells will provide insight into cellular basis of the disease.[1]

References

  1. Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients. Sathasivam, K., Woodman, B., Mahal, A., Bertaux, F., Wanker, E.E., Shima, D.T., Bates, G.P. Hum. Mol. Genet. (2001) [Pubmed]
 
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