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ToxSci Advance Access published online on November 8, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl142
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 31, 2006
Accepted October 20, 2006

Environmental Toxicology

Expression Profiling of Heat Stress Effects on Mice Fed Ergot Alkaloids

S. Bhusari 1, Z. Liu 1, L. B. Hearne 2, D. E. Spiers 1, W. R. Lamberson 1, and E. Antoniou 1 *

1 Division of Animal Sciences, University of Missouri-Columbia, Columbia, MO 65211
2 Department of Statistics, University of Missouri-Columbia, Columbia, MO 65211

* To whom correspondence should be addressed.
E. Antoniou, E-mail: AntoniouE{at}missouri.edu


  Abstract

Fescue toxicosis affects wild and domestic animals consuming ergot alkaloids contained in tall fescue forage infected with the endophytic fungus, Neotyphodium coenophialum. When animals are consuming infected fescue forage during periods of elevated ambient temperatures (summer), a range of phenotypic disorders collectively called summer slump is observed. It is characterized by hyperthermia, with an accompanying decrease in feed intake, growth, milk yield and reproductive fitness. Laboratory mice also exhibit symptoms of fescue toxicosis at thermoneutral temperature, as indicated by reduced growth rate and reproductive fitness. Our goal was to characterize the differences in gene expression in liver of mice exposed to summer-type heat stress (HS) and infected fescue (E+) when compared to mice fed infected fescue at thermoneutral temperature. Mice were fed E+ diet under HS (34 ± 1°C; n = 13; E+HS) or thermoneutral (TN) conditions (24 ± 1°C; n = 14; E+TN) for a period of two weeks between 47 to 60 d of age. Genes differentially expressed between E+HS versus E+TN were identified using DNA microarrays. Forty-one genes were differentially expressed between treatment groups. Expressions of eight genes were measured using quantitative real-time PCR. Genes coding for phase I detoxification enzymes were up-regulated in E+HS mouse liver. This detoxification pathway is known to produce reactive oxidative species. We observed an up-regulation of genes involved in the protection against reactive oxidative species. Key genes involved in de novo lipogenesis and lipid transport were also up-regulated. Finally, genes involved in DNA damage control and unfolded protein responses were down-regulated.

Keywords: Methods - microarray; Environmental Toxicology; Gene Expression/Regulation.
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[Abstract] [Full Text] [PDF]


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