Project description:Fescue toxicosis is a disease of wild and domestic animals grazing on fescue pasture infected with the endophytic fungus, Neotyphodium Coenophialum. Mice, previously selected for increased sensitivity to endophyte-infected fescue seed diets indicated by slow weight gain, were used to study the effects of fescue toxicosis on hepatic gene expression. Liver genes differentially expressed due to fescue toxins were studied using DNA microarray. A two-stage ANOVA of microarray data identified forty differentially expressed genes between mice fed endophyte-infected (E+) and endophyte-free (E-) fescue seeds. Significant Analysis of Microarray (SAM) analysis identified 9 genes as differentially expressed between treatment groups. Hierarchical clustering with the 40 genes identified by ANOVA clearly separate the mice according to their diets, with 100% confidence as computed by bootstrap analysis. Expressions of eleven genes were verified using quantitative real-time PCR (qPCR). The E+ diet resulted in downregulation of genes involved in sex-steroid metabolism pathway, genes involved in cholesterol and lipid metabolism. Keywords = Endophyte Keywords = Fescue Toxicosis Keywords = microarray Keywords: repeat sample
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Intake of ergot alkaloids associated with endophyte-infected fescue (E+) has adverse effects on animal health and productivity, which is collectively, termed fescue toxicosis. These effects are exacerbated under hot and humid (summer) conditions. A rat model for this condition was used to evaluate the effect of endophytic toxins on hepatic gene expression under acute (three days) heat stress (HS). Core temperature (Tc) was monitored continuously in rats (n=12) implanted with telemetric transmitters. Rats were fed ad libitum an E+ diet and maintained under thermoneutral (TN) conditions (21 ˚C) for five days, followed by TN or HS conditions (31 ˚C) for three days. Feed intake (FI) and body weight (BW) were measured daily. Both E+ and HS induced alterations in hepatic genes were evaluated using DNA microarrays. Intake of E+ reduced FI and BW under TN and HS conditions from pretreatment level, with greater reduction occurring during HS period. Core temperature at TN did not change from pretreatment level, but increased during HS. Genes associated with ATP synthesis, immune function, chaperone activity, and antioxidant function were reduced in E+HS vs E+TN. Present findings suggest that rats respond to E+ during heat stress by inducing hepatic CYP3A4 expression and suppressing chaperone, antioxidant and immune systems, which could ultimately increase the stress resulting in various pathological abnormalities. Keywords: Stress response
Project description:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.