Growth and physiological responses to toxicosis in lines of mice selected for resistance or susceptibility to endophyte-infected tall fescue in the diet.

Abstract

In three experiments, mice from lines selected for resistance (R) or susceptibility (S) to growth depression from endophyte-infected fescue seed in the diet were fed diets containing infected (E+) or non-infected (E-) seed. Activities of liver enzymes known to participate in oxidation, reduction, or hydrolysis or in conjugation of xenobiotics were measured in these mice. In all experiments, E+ caused greater reduction in initial ADG of S than of R mice. In Exp. 1, liver cytochromes P450 and b5 activities were not affected by line, diet, or their interaction. These enzymes were not evaluated in subsequent experiments. In all experiments, glutathione-S-transferase (GST) and uridine diphosphate glucuronosyltransferase (GRT) activities differed between lines. Resistant mice had significantly higher GST activity on both diets in Exp. 1, on E- in Exp. 2, and on E+ in Exp. 3. Resistant mice had higher GRT activities on E+ in Exp. 1, on E- in Exp. 2, but after 4 wk on either diet in Exp. 3. Before test diets were imposed in Exp. 3, GST and GRT activities were higher in R-line mice. Divergent selection created lines that differed in response to tall fescue in the diet. Postweaning growth of resistant mice was less severely depressed by E+, although susceptible mice later expressed compensatory gain. Activities of two detoxification enzymes generally were higher in livers from R-line mice, suggesting a biochemical mechanism for the difference. Using such traits, it may be possible to select ruminants for resistance to fescue toxicosis.

Growth and hepaticin vitrometabolism of ergotamine in mice divergently selected for response to endophyte toxicity

“…The lines were provided ad libitum access to rodent food. Environmental conditions were similar to those described in Hohenboken et al (1997). Forty female mice each of the resistant and susceptible lines were mated to a male from their same line.…”

“…Lines of endophyte-resistant and -susceptible mice were established previously from Harlan Sprague-Dawley male and female ICR mice (Hohenboken and Blodgett 1997). Lines were maintained as separate yet with no further selection for the last 13 generations, a strategy referred to as 'relaxed selection'.…”

“…Laboratory mice may serve as a model to detect genetic differences between animals that are resistant and susceptible to fescue toxicosis since mice exposed to an Eþ diet have a reduced reproductive capacity in pregnancy and litter size (Zavos et al 1987a(Zavos et al , 1987bGodfrey et al 1994) and a depressed growth of pups due to reduced suckling performance of the dam (Zavos et al 1988). The experiments performed in the present study are a continuation of research where mice with a measurable genetic divergence in susceptibility to endophyte toxicity served as a model to study the physiological effects and metabolism of ergot alkaloids (Miller et al 1994;Hohenboken and Blodgett 1997;Wagner et al 2000). A long-term goal of this research is the identification of biochemical parameters that differ between the lines which could be applied to livestock to measure susceptibility amongst individuals, herds, breeds and species.…”

“…Previous work has shown that resistant mice have higher Phase I (Arthur et al 2003) and Phase II (glutathione S-transferase (GST) and UDP-glucuronosyl S-transferase (UDPGT)) (Hohenboken and Blodgett 1997;Wagner et al 2000) enzyme activities than susceptible mice. This suggests that both Phase I and II enzymes play a role in the physiological mechanism imparting resistance to endophyte toxicity.…”

Review of genetic studies of susceptibility to facial eczema in sheep and dairy cattle

“…Genetic differences in response to the challenge among sire groups of cattle have been reported (Lipsey et al 1992) and breed differences in weight gain have been recorded in affected cattle in Arkansas (Morrison et al 1988). Related studies of ergovaline susceptibility in mice have been carried out, where heritable differences in tolerance to ergovaline in the diet were found among selection lines (Hohenboken and Blodgett, 1997); following an artificial challenge with sporidesmin in the selected lines, some of the genetic variation among lines for ergovaline tolerance was found to be in common with that for resistance to FE (Hohenboken et al 2000). This suggests that some genes for the detoxification of ergovaline and sporidesmin may be in common, as was the case of lolitrem and sporidesmin, described earlier.…”