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Publication : Global disruption of the cerebellar transcriptome in a Down syndrome mouse model.

First Author  Saran NG Year  2003
Journal  Hum Mol Genet Volume  12
Issue  16 Pages  2013-9
PubMed ID  12913072 Mgi Jnum  J:95709
Mgi Id  MGI:3526832 Doi  10.1093/hmg/ddg217
Citation  Saran NG, et al. (2003) Global disruption of the cerebellar transcriptome in a Down syndrome mouse model. Hum Mol Genet 12(16):2013-9
abstractText  Trisomy 21 (Down syndrome) results in cerebellar dysmorphology with direct parallels in the Ts65Dn mouse. Despite pronounced changes in morphology, cerebellar function is not markedly different. As a first test of whether those cerebellar cells that have survived to adulthood in trisomic mice are equivalent to euploid cells, we used microarrays to assess the trisomic and euploid cerebella. Trisomic and euploid transcriptomes were robustly distinguished. Changes in expression of individual genes were very subtle, but the differences in respective transcriptome phenotypes extended deeply into the set of nearly 7000 probes (genes) located throughout the genome. In contrast to deterministic models of gene action in trisomy, examination of the discriminating genes in two independent experiments suggests that the global perturbation includes a significant stochastic component. Thus, dosage imbalance of 124 genes in Ts65Dn mice alters the expression of thousands of genes to create a variable trisomic transcriptome. This global destabilization has important implications for approaches to ameliorative therapies in Down syndrome.
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