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E-GEOD-34442 - The Autonomous Hepatocyte Clock Controls Acetaminophen Bioactivation and Chronotoxicity [Liver]

Status
Released on 30 August 2013, last updated on 2 June 2014
Organism
Mus musculus
Samples (48)
Array (1)
Protocols (7)
Description
The diurnal variation in acetaminophen (APAP) hepatotoxicity (“chronotoxicity”) is thought to be due to oscillations in xenobiotic metabolism that are influenced by the circadian phases of feeding or fasting. Because of APAP’s relevance to human poisoning, we set out to determine the relative contributions of the central clock in the SCN and the autonomous clock in the hepatocyte in modulating the chronotoxicity of APAP. Using a conditional null allele of Mop3 (ArntL, Bmal1) we are able to delete the clock from hepatocytes while keeping the central and other peripheral clocks intact (eg, those controlling food intake). Our data from this hepatocyte-null mouse model suggests that, while the central circadian clock modulates some detoxification pathways indirectly by driving activity patterns and feeding rhythms, the autonomous hepatocyte circadian clock controls major aspects of APAP bioactivation independent of feeding rhythms. 10-20 week old Mop3fxfx mice positive or negative for Cre-recombinase driven by the albumin promoter, housed in 12 hour light:12 dark, ad lib feeding and drinking conditions were sacrificed every four hours over two separte days beginning at ZT0. A two color, reference design experiment in which liver RNA from at least 3 mice per timepoint were pooled and labeled with Cy3 and hybridized according to Agilent protocols against a reference pool of RNA madeup from respective tissue taken from 10 week Mop3fxfx and Mop3fxfxCreAlb mice which was labeled with Cy5.
Experiment type
transcription profiling by array 
Contacts
Brian P Johnson, Chris A Bradfield
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-34442.idf.txt
Sample and data relationshipE-GEOD-34442.sdrf.txt
Raw data (2)E-GEOD-34442.raw.1.zip, E-GEOD-34442.raw.2.zip
Processed data (1)E-GEOD-34442.processed.1.zip
Array designA-MEXP-724.adf.txt
Links