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Microarray analysis of mouse cerebral cortex from brain-specific Bmal1 knockout and Per1;Per2 double mutant mice at 2 timepoints

ABSTRACT: The aim of this study was to examine the effect of genetic disruption of the circadian clock on gene expression in the cortex across timepoints. Circadian clock protein regulate many critical aspects of cellular function, and Bmal1 knockout mice develop severe neuroinflammation, suggesting a role for circadian clock gene in brain homeostatic function. We compared brain-specific Bmal1 KO mice (Nestin-Cre;Bmal1(flox/flox) with Per1/2 double mutant mice, in order to assess the effects of deletion of the positive and negative limbs of the core clock. 11mo Cre-, NestinCre+/-;Bmal1(fx/fx), or Per1brdm,Per2brdm mice were entrained to 12h light:dark conditions with lights on at 6am for one month, then placed in constant darkness for 24 hours, after which mice were harvested at 6am (CT6) or 6pm (CT18), still in the dark. Mice were anesthetized in the dark, then perfused briefly with PBS+heparin. The brain was then quickly dissected on a cold surface, and the cerebral cortex flash frozen in liquid nitrogen. Cortex samples were mechanically dissociated with a Qiashredder device, then extracted with chloroform and diluted in 70% ethanol. RNA was extracted using Qiagen RNEasy kit according to manufacturers specifications. cDNAs were chemically labeled with Kreatech ULS RNA labeling kit (Kreatech Diagnostics) and Cy5-labeled cDNAs were hybridized to Agilent Mouse v2 4x44K microarrays (G4846A-026655).

ORGANISM(S): Mus musculus

SUBMITTER: Erik Musiek

PROVIDER: E-MTAB-7151 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptomic analysis of cortex tissue from neuron-specific Bmal1 KO mice

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Microarray of hippocampus from 5mo wt, Bmal1 KO and Nr1d1 (Rev-Erb-alpha) KO mice at a single timepoint

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Targeted disruption of BMAL1 in the peripheral reproductive axis results in infertility in female mice.

Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology, and its disruption results in infertility. In an effort to identify the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the regulation of ovarian steroidogenic acute regulator (StAR) and its role in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis leads to lower levels of StAR mRNA, and lower progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants results in 100% fertility. Our study suggests that ovarian Bmal1 is an essential peripheral clock governing implantation and fertility in female mice. Ten week old female Bmal1fxfx mice positive or negative for Cre-recombinase driven by the sf-1 promoter, housed in 12 hour light:12 dark, ad lib feeding and drinking conditions were sacrificed at ZT12 on 3.5dpc (3.5 days post copulation). For each array analysis, a pool of 3 RNA samples from 3 individual Bmal1fx/fxCresf-1 ovaries labeled with cy3 were co-hybridized with a pool of 3 RNA samples from Bmal1fx/fx ovaries labeled with cy5, according to Agilent protocols.

2013-02-01 | E-GEOD-38365 | biostudies-arrayexpress

Gene Model 129 (Gm129) Encodes a Novel Transcriptional Repressor that Modulates Circadian Gene Expression

2014-01-07 | GSE53828 | GEO

Targeted disruption of BMAL1 in the peripheral reproductive axis results in infertility in female mice

Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology,and when disrupted results in infertility. In an effort to establish the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the ovaries, including regulation of ovarian lipid biosynthetic or metabolic processes and their roles in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis reducesleads to affected transcripts in steroidogenic pathways for the LH receptor , and lowers progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants rescues fertility. Our study demonstrates the significance of ovarian Bmal1 as an overriding influence in experimental models of infertility. A time series was performed in time-mated C57Bl/6J mice to identiy oscillating transcripts. During the peak and trough of the majority of transcripts (ZT0 and ZT12) samples from Bmal1fx/fx Sf1Cre mice and control litermates as well and global Bmal1 nulls were also analyzed. The tissue types (ovary, pituitary) are not comparable.

2014-10-01 | E-GEOD-48758 | biostudies-arrayexpress

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