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| Status |
Public on Aug 02, 2012 |
| Title |
Gene expression changes in Dhcr7 knockout brain, lung and liver at E18.5 compared to wild-type embryos |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The genetic defect underlying the human Smith-Lemli-Opitz dysmorphological disorder is loss-of-function mutations affecting the cholesterol synthesis enzyme dehydrocholesterol delta7 reductase, DHCR7. Dhcr7 knockout mice recapitulate the biochemical characteristics, but all knockout pups die within 14h of birth. Tissues of knockout mice accumulate the precursor sterol, 7-dehydrocholesterol, and show reduced levels of cholesterol (J. Clin. Invest. (2001) 108: 905-915). We compared the global gene expression changes in lung, liver and brain from knockout mice to those seen from organs harvested from same-pregnancy wild-type embryos, harvested before birth (E18.5). Since the P0 knockout pups die, we expected that there would be significant changes in gene expression between knockout and wild-type organs, and further comparing the altered genes in common to brain, lung and liver would point to a common mechanistic pathway where disruption of normal sterol synthesis in all cells leads to pathophysiology.
Remarkably, these data show that the global gene expression between knockout and wild-type organs is hardly altered, despite the complete loss of cholesterol synthesis. There are so few genes that are altered, and furthermore, those that are altered are very limited in sharing similarities in all three tissues. This suggests that disorganized gene expression is not the cause of the early neonatal lethality.
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| Overall design |
Dhcr7+/- females were mated with Dhcr+/- males, and timed pregnancy obtained. At E18.5, pregnant dams were sacrificed, and embryos harvested, organs removed and RNA extracted, and all embryos were genotyped. Matching wild-type and knockout embryos were taken from each pregnancy, and two females yielded all genotypes used herein.
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| Contributor(s) |
Patel SB, Yu H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 01, 2012 |
| Last update date |
Aug 03, 2012 |
| Contact name |
Michael Falduto |
| E-mail(s) |
mfalduto@genusbiosystems.com
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| Phone |
847-291-9602
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| Organization name |
GenUs BioSystems, Inc.
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| Street address |
1808 Janke, Unit M
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| City |
Northbrook |
| State/province |
IL |
| ZIP/Postal code |
60062 |
| Country |
USA |
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| Platforms (1) |
| GPL8063 |
GE Healthcare/Amersham Biosciences CodeLink™ Mouse Whole Genome Bioarray |
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| Samples (18)
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| GSM979616 |
Wild-type brain, F294 |
| GSM979617 |
Wild-type lung, F294 |
| GSM979618 |
Wild-type liver, F294 |
| GSM979619 |
Wild-type brain, F295 |
| GSM979620 |
Wild-type lung, F295 |
| GSM979621 |
Wild-type liver, F295 |
| GSM979622 |
Dhcr7 knockout brain, F297 |
| GSM979623 |
Dhcr7 knockout lung, F297 |
| GSM979624 |
Dhcr7 knockout liver, F297 |
| GSM979625 |
Dhcr7 knockout brain, F299 |
| GSM979626 |
Dhcr7 knockout lung, F299 |
| GSM979627 |
Dhcr7 knockout liver, F299 |
| GSM979628 |
Dhcr7 knockout brain, F300 |
| GSM979629 |
Dhcr7 knockout lung, F300 |
| GSM979630 |
Dhcr7 knockout liver, F300 |
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| Relations |
| BioProject |
PRJNA171752 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE39811_RAW.tar |
24.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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