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| Status |
Public on Sep 05, 2013 |
| Title |
Analysis of the Cerebral Cortex and Hippocampus Transcriptome Reveals Unique Molecular Changes in the Ts1Cje Mouse Model of Down Syndrome |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Down syndrome is characterized by a complex phenotype that includes developmental disabilities and congenital anomalies. The molecular origin of these abnormalities is poorly understood. The objective of this study is to analyze whole transcriptome changes in the cortex and hippocampus of the Ts1Cje mouse model of Down syndrome to identify signaling pathways and cellular processes that are consistently perturbed in both brain regions. These pathways will offer a new opportunity for therapeutic interventions to improve cognition in Down syndrome.
We refined the translocation breakpoints of MMU12 and MMU16 described previously and established the brain transcriptional map for both monosomic (MMU12) and trisomic (MMU16) regions in Ts1Cje mice. We showed that the hippocampus have more differentially regulated genes, however, the directions of regulation of these genes were generally similar in both brain regions. The secondary genome-wide effect implicated genes known to play major roles in cellular functions that are affected in Down syndrome. Functional analyses highlighted the importance of NFAT signaling, oxidative stress, neuroinflammation, hormone metabolism and olfactory perception via G-protein signaling. This study offers novel targets for therapeutic intervention in Down syndrome.
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| Overall design |
We analyzed the cerebral cortex and hippocampus whole transcriptome from 8-10 weeks old Ts1Cje (n=6) and wild-type (n=5) using Affymetrix mouse gene 1.0 ST array. Data were normalized and analyzed to identify and accurately map genes that are significantly differentially expressed. Functional analyses were performed using GSEA and DAVID to better characterize cellular processes and pathways that are consistently affected in both brain regions.
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| Contributor(s) |
Guedj F, Pennings JA, Wick HC, Slonim DK, Bianchi DW |
| Citation(s) |
24916381, 25975229 |
| |
| Submission date |
Aug 07, 2013 |
| Last update date |
Jul 18, 2019 |
| Contact name |
Heather C Wick |
| E-mail(s) |
[email protected]
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| Organization name |
Tufts University
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| Department |
Department of Computer Science
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| Street address |
161 College Ave
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| City |
Medford |
| State/province |
MA |
| ZIP/Postal code |
02155 |
| Country |
USA |
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| Platforms (1) |
| GPL13730 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [CDF: MoGene10stv1_Mm_ENTREZG_14.1.0] |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA214547 |
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