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| Status |
Public on Apr 30, 2012 |
| Title |
Mice lacking circadian transcriptional activator Clock exhibit dramatic changes in renal excretory rhythms |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation.
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| Overall design |
We examined the temporal profiles of gene expression in mouse whole kidney. Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT – Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on pools of RNA composed of equivalent amounts of RNA prepared from teo or three animals at each ZT time-point.
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| Contributor(s) |
Nikolaeva S, Centeno G, Pradervand S, Zavadova V, Tokonami N, Maillard M, Bonny O, Firsov D |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Feb 16, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Sylvain Pradervand |
| E-mail(s) |
[email protected]
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| Phone |
+41 21 692 39 08
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| Organization name |
UNI Lausanne
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| Department |
CIG
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| Lab |
DNA Array Facility
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| Street address |
Genopode
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| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA137287 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27366_RAW.tar |
88.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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