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| Status |
Public on Aug 16, 2011 |
| Title |
Down-regulation of cholesterol biosynthesis in forebrains of ERCC1-deficient mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Several genetic defects of the nucleotide excision repair (NER) pathway, including deficiency of the Excision Repair Cross-Complementing rodent repair deficiency, complementation group 1 (ERCC1), result in pre-mature aging, impaired growth, microcephaly and delayed development of the cerebellum. Such a phenotype also occurs in ERCC1-knockout mice which survive for up to 4 weeks after birth. Therefore, we analyzed cerebellar and hippocamapal transcriptomes of these animals at 3 weeks of age to identify the candidate mechanisms underlying brain consequences of reduced ERCC1 activity.
Results: In the cerebellum, the most prominent change was upregulation of genes that are associated with gliosis. Although Purkinje cell degeneration has been reported in some mouse strains with NER impairment, Purkinje cell transcriptome was mostly unaffected by the ERCC1 knockout. In the hippocampus, the gliosis response was minimal. Instead, there was an extensive downregulation of genes related to lipid metabolism including several enzymes of the cholesterol biosynthesis pathway as well as lipoproteins and plasma membrane proteins. Reduced expression of the cholesterol biosynthesis pathway genes was also present in the neocortex of adult mice whose ERCC1 gene was replaced by a mutant allele with a partial activity.
Conclusions: Downregulation of forebrain cholesterol biosynthesis genes is a newly identified consequence of ERCC1 deficiency. Its presence in adult mice suggests that it is not a secondary consequence of brain growth impairment. Instead, reduced cholesterol biosynthesis may contribute to such an impairment as well as affect function of mature synapses.
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| Overall design |
We analyzed the hippocampus and cerebellum from three Ercc1-/- and three WT littermates using the Affymetrix Mouse Genome 430_2.0. Data was analyzed using the dChip DNA-Chip analyzer software .
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| Contributor(s) |
Smith SC, Robinson AR, Zheng J, Niedernhofer LJ, Hetman M |
| Citation(s) |
22245387 |
| Submission date |
Aug 04, 2011 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Scott Carl Smith |
| Organization name |
Kentucky Spinal Cord Injury Research Center
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| Department |
Neurosurgery
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| Lab |
Neural Signaling
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| Street address |
511 S. Floyd St.
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| City |
Louisville |
| State/province |
KY |
| ZIP/Postal code |
40202 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA144745 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31199_Cerebella.txt.gz |
11.9 Kb |
(ftp)(http) |
TXT |
| GSE31199_Cerebella_dChip.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE31199_Hippocampus.txt.gz |
9.4 Kb |
(ftp)(http) |
TXT |
| GSE31199_Hippocampus_dChip.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE31199_RAW.tar |
46.9 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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