Project description:Mouse models of Fetal Alcohol Spectrum Disorder can be used to assess molecular changes underlying the disorder. Neonatal ethanol exposure in mice can be used to model third trimester ethanol exposure in humans.
Project description:Mouse models of Fetal Alcohol Spectrum Disorder can be used to assess molecular changes underlying the disorder. Neonatal ethanol exposure in mice can be used to model third trimester ethanol exposure in humans.
Project description:Mouse models of Fetal Alcohol Spectrum Disorder can be used to assess molecular changes underlying the disorder. Neonatal ethanol exposure in mice can be used to model third trimester ethanol exposure in humans. Mice were injected with 2.5 g/kg twice on each of postnatal days 4 and 7. Mice were allowed to reach postnatal day 70, at which time whole-hippocampus was isolated and snap frozen. Tissue was thawed and RNA was isolated. RNA run on affymetrix gene expression array according to standard protocol. Each array was a pool of three mice, for a total n=9 ethanol-exposed and 9 control mice. All mice were male.
Project description:Moderate alcohol exposure during pregnancy can result in a heterogeneous range of neurobehavioural and cognitive effects, termed fetal alcohol spectrum disorders (FASD). We have developed a mouse model of FASD that involves moderate ethanol exposure throughout gestation achieved by voluntary maternal consumption. This model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that this leaves a long-term footprint on the adult brain. However, the long-term effects of prenatal ethanol exposure on brain gene expression, when behavioural phenotypes are apparent, are unclear. We used a microarray experiment and focused on the genes identified by both to evaluate the genome-wide alterations to the adult brain transcriptome caused by prenatal ethanol exposure. To generate samples, female C57BL/6J mice were given ethanol injections (2.5g/kg of ethanol in saline) twice on gestational days 8 and 11 to produce acute ethanol exposure effects. Control females were injected with the same volume of saline. Females were mated. Whole brain RNA from adult (postnatal day 70) male ethanol-exposed offspring was extracted. RNA samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice).
Project description:This experiment is an application of MeDIP-seq on hippocampus in a mouse model of fetal alcohol spectrum disorder (FASD). Here, we investigate genome-wide changes in DNA methylation in six C57BL/6 mice (3 ethanol-exposed and 3 saline-exposed). Mice were injected with either ethanol or saline on postnatal days 4 and 7, with hippocampal DNA methylation assessed on postnatal day 21. Across the six mice, there are 151,911 MeDIP peaks mapped to “intergenic”, “gene body”, or “promoter” based on the DNAm peaks proximity to a gene. Of these locations, 18,992 regions (16,374 intergenic, 1,887 gene body, 661 promoter) were common in all six mice (113,532 total) and can be combined for further analysis.
Project description:Moderate alcohol consumption during pregnancy can result in a heterogeneous range of neurobehavioural and cognitive effects, termed fetal alcohol spectrum disorders (FASD). We have developed a mouse moder of FASD that involves moderate ethanol exposure throughout gestation achieved by voluntary maternal consumption. This model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that this leaves a long-term footprint on the adult brain. However, the long-term effects of prenatal ethanol exposure on brain gene expression, when behavioural phenotypes are apparent, are unclear. We used two independent microarray experiments and focused on the genes identified by both to evaluate the genome-wide alterations to the adult brain transcriptome caused by prenatal ethanol exposure via moderate maternal drinking. To generate samples, two independent groups of female C57BL/6J mice were given access to 10% ethanol in water or water only. Control females had access to water only. Females were mated and continued to drink from gestational day 0 to pup postnatal day 10. Whole brain RNA from adult (postnatal day 70) male ethanol-exposed offspring was extracted. For experiment 1, RNA samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice). For experiment 2, RNA from two mice were pooled per chip and three arrays per treatment were used (3 control, 3 ethanol, total n=12 mice).
Project description:Purpose: To investigate the effect that acute ethanol tretament (5 g/kg) has on the brain transcriptome and relate that to ethanol-related behaviors. Methods: Male LXS recombinant inbred mice (40 strains; n=2 or 3 per strain) were treated with saline or ethanol (i.p.; 5 g/kg). Paired-end RNA-seq methods were employed to assess mRNA expression in whole brain 8 hours after the treatment. Results: The expression of thousands of transcripts was altered by the ethanol treatment. Thousands of expression QTLs (eQTLs) were mapped. A large percentage of the eQTLs were unique to the treatment.
Project description:Moderate alcohol exposure during pregnancy can result in brain gene expression changes in resulting offspring. We have developed a mouse model of FASD that involves moderate ethanol exposure in mid-gestation (trimester 2 equivalent) achieved by injections of ethanol. We have previously shown that this model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that there will be gene expression changes immediately following acute ethanol exposure in the fetal brain. We used a microarray experiment and focused on the genes identified to evaluate the genome-wide alterations to the fetal brain transcriptome caused by prenatal ethanol exposure. To generate samples, female C57BL/6J mice were given ethanol injections (2.5g/kg of ethanol in saline) twice on gestational days 14 and 16 to produce acute ethanol exposure effects. Control females were injected with the same volume of saline. Dams were sacrified on gestational day 16, following ethanol exposure, and whole brains from fetuses were then extracted. RNA was isolated from brain tissue and samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice).
Project description:Timed pregnant C57Bl6 mice were exposed to ethanol during a critical period, gestational day 15 to 18, of cerebral cortical development to identify gene expression changes in the cerebral cortex of developing fetus due to this ethanol exposure Keywords: Compared animals exposed to ethanol (alcohol fed group) to a pair-fed control group and both groups were normalized to a control group (animals fed adlibitum)