Genome wide anaylsis of transcriptome modifications in male mice exposed to tributyltin during development
Ontology highlight
ABSTRACT: Purpose: To identify alterations induced by developmental exposure to tributyltin at different stages of life Methods: Dams were treated with tributyltin during gestation and lactation in drinking water and pups were euthanized at different ages Results: We identified a number of changes in transcriptomic activity in 5 month, and ten month old pups after tributyltin exposure. Male animals exposed to tributyltin also developed fatty liver 5 months of age and adenomas of the liver at ten months of age.
Project description:We compared the gene expressions of the intestine, liver and spleen tissues between mice at 4 months of age and mice at 28 months of age. We used microarrays to examine the age-related changes of gene expressions of the jejunum, ileum, distal colon, liver and spleen in mice. Abbreviations used: C, 28-month-old mice; Y, 4-month-old mice.
Project description:Werner syndrome is a progeroid disorder caused by mutations in a protein (Wrn) containing both a DNA exonuclease and DNA helicase domain. In this study, we identified proteins that exhibit abundance differences in the serum and liver tissue of wild type and Wrn mutant mice at four and ten months of age using a label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach. Although Wrn mutant mice exhibited fatty liver by the age of ten months, gene ontology analysis on differentially expressed proteins revealed sexual dimorphism. Alterations only in specific immunoglobulin molecules were common biomarkers in the fatty liver and serum of both Wrn mutant females and males with age.
Project description:RNA sequencing of mouse liver and kidney. UMHET pups were treated with diet containing encapsulated rapamycin or encapsulating material as a control from birth to 45 days of age, and tissues were collected at 2, 20-22 and 27-29 months of age from both males and females, and 3-5 samples per age, sex and treatment were sequenced.
Project description:Tributyltin (TBT) accumulates at higher levels in the liver than in any other organ, and it acts as a hepatotoxic agent. Most of the available studies on TBT have focused on observations at the cellular level, and studies at the level of genes and proteins have been limited; therefore, the information concerning possible mechanisms of TBT-induced adverse health effects remains scarce and inconclusive. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702.
Project description:To study the ontogeny of pharmacological relevant genes, such as, drug targets, transporters and metabolic enzymes, six wild-type C57BL/6JCrl female mice were sacrified at ten different age points, in order to capture potential transcriptomic switches as the mice progresses from newborn to infant, from infant to teenager, from teenager to adult, and finally from adult to old-adult (P1 - 1 day old; 1W - 1 week old; 2W - 2 weeks old; 3W - 3 weeks old; 1M - 1 month old; 2M - 2 months old; 3M - 3 months old; 6M - 6 months old; 1Y - 1 year old; and 2Y - 2 years old). Liver, heart, kidney, lungs and brain were extracted from all 60 females in the study, and liver samples were processed for RNA extraction. Overall, 8.3% of pharmacological relevant genes changed their expression with age, of which 57% were metabolic enzymes, like Cyp2c29 and Fmo3, and 22% were transporters.
Project description:Adipose, liver, and skeletal muscle tissue from 6-month and 12-month CC-RIX cohorts underwent transcriptomic profiling. CC-RIX cohorts were exposed to sensitizer (HFHS diet) and a widely used pharmaceutical intervention (metformin). Chow (control) or high fat high sugar (HFHS) diet started at 6 weeks of age.. At six months of age, a subset of mice from each chow group and of each sex were euthanized for tissue collection. At 7 months of age, half of the remaining mice in each diet treatment group will receive metformin treatment. In a subset of the 12 month cohort animals, metformin (5 mg/mL) was delivered ad libitum in the drinking water (Chang, Moro et al. 2018). Terminal phenotyping and tissue collection was done at 12 months of age.
Project description:Adipose, liver, and skeletal muscle tissue from 6-month and 12-month CC-RIX cohorts underwent transcriptomic profiling. CC-RIX cohorts were exposed to sensitizer (HFHS diet) and a widely used pharmaceutical intervention (metformin). Chow (control) or high fat high sugar (HFHS) diet started at 6 weeks of age.. At six months of age, a subset of mice from each chow group and of each sex were euthanized for tissue collection. At 7 months of age, half of the remaining mice in each diet treatment group will receive metformin treatment. In a subset of the 12 month cohort animals, metformin (5 mg/mL) was delivered ad libitum in the drinking water (Chang, Moro et al. 2018). Terminal phenotyping and tissue collection was done at 12 months of age.
Project description:Adipose, liver, and skeletal muscle tissue from 6-month and 12-month CC-RIX cohorts underwent transcriptomic profiling. CC-RIX cohorts were exposed to sensitizer (HFHS diet) and a widely used pharmaceutical intervention (metformin). Chow (control) or high fat high sugar (HFHS) diet started at 6 weeks of age.. At six months of age, a subset of mice from each chow group and of each sex were euthanized for tissue collection. At 7 months of age, half of the remaining mice in each diet treatment group will receive metformin treatment. In a subset of the 12 month cohort animals, metformin (5 mg/mL) was delivered ad libitum in the drinking water (Chang, Moro et al. 2018). Terminal phenotyping and tissue collection was done at 12 months of age.
Project description:We found that deleting Pten in Albumin expressing cells results in liver steatosis as early as 1 month of age. The mice develop hyperplasia and tumor phenotypes starting at 7-8 months of age. At 12 months and beyond, all mice develope spontanous liver tumors of mixed lineage phenotypes dihydrocollidine (DDC) shows that the primary effect of AKT2 loss is attenuation of hepatic injury and not inhibition of progenitor cell proliferation in response to injury.