The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome

Dauphinot, L., Lyle, R., Rivals, I., Dang, M.T., Moldrich, R. X., Golfier, G., Ettwiller, L., Toyama, K., Rossier, J., Personnaz, L., Antonarakis, S. E., Epstein, C. J., Sinet, P. M. and Potier, M. C. (2005) The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome. Human Molecular Genetics, 14 3: 373-384. doi:10.1093/hmg/ddi033


Author Dauphinot, L.
Lyle, R.
Rivals, I.
Dang, M.T.
Moldrich, R. X.
Golfier, G.
Ettwiller, L.
Toyama, K.
Rossier, J.
Personnaz, L.
Antonarakis, S. E.
Epstein, C. J.
Sinet, P. M.
Potier, M. C.
Title The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2005-02
Sub-type Article (original research)
DOI 10.1093/hmg/ddi033
Volume 14
Issue 3
Start page 373
End page 384
Total pages 12
Place of publication Oxford, England
Publisher Oxford Univ Press
Language eng
Subject 100401 Gene and Molecular Therapy
Abstract The central nervous system of persons with Down syndrome presents cytoarchitectural abnormalities that likely result from gene-dosage effects affecting the expression of key developmental genes. To test this hypothesis, we have investigated the transcriptome of the cerebellum of the Ts1Cje mouse model of Down syndrome during postnatal development using microarrays and quantitative PCR (qPCR). Genes present in three copies were consistently overexpressed, with a mean ratio relative to euploid of 1.52 as determined by qPCR. Out of 63 three-copy genes tested, only five, nine and seven genes had ratios >2 or <1.2 at postnatal days 0 (P0), P15 and P30, respectively. This gene-dosage effect was associated with a dysregulation of the expression of some two-copy genes. Out of 8258 genes examined, the Ts1Cje/euploid ratios differed significantly from 1.0 for 406 (80 and 154 with ratios above 1.5 and below 0.7, respectively), 333 (11 above 1.5 and 55 below 0.7) and 246 genes (59 above 1.5 and 69 below 0.7) at P0, P15 and P30, respectively. Among the two-copy genes differentially expressed in the trisomic cerebellum, six homeobox genes, two belonging to the Notch pathway, were severely repressed. Overall, at P0, transcripts involved in cell differentiation and development were over-represented among the dysregulated genes, suggesting that cell differentiation and migration might be more altered than cell proliferation. Finally, global gene profiling revealed that transcription in Ts1Cje mice is more affected by the developmental changes than by the trisomic state, and that there is no apparent detectable delay in the postnatal development of the cerebellum of Ts1Cje mice.
Keyword Biochemistry & Molecular Biology
Genetics & Heredity
Granule Cell-differentiation
Gene-expression
Behavioral Abnormalities
Amyloid Formation
Ts65dn
Transthyretin
Phenotypes
Mutation
Region
Brain
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
 
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Created: Fri, 25 Jan 2008, 16:26:45 EST