Using Domestic and Free-Ranging Arctic Canid Models for Environmental Molecular Toxicology Research

Abstract

The use of sentinel species for population and ecosystem health assessments has been advocated as part of a One Health perspective. The Arctic is experiencing rapid change, including climate and environmental shifts, as well as increased resource development, which will alter exposure of biota to environmental agents of disease. Arctic canid species have wide geographic ranges and feeding ecologies and are often exposed to high concentrations of both terrestrial and marine-based contaminants. The domestic dog (Canis lupus familiaris) has been used in biomedical research for a number of years and has been advocated as a sentinel for human health due to its proximity to humans and, in some instances, similar diet. Exploiting the potential of molecular tools for describing the toxicogenomics of Arctic canids is critical for their development as biomedical models as well as environmental sentinels. Here, we present three approaches analyzing toxicogenomics of Arctic contaminants in both domestic and free-ranging canids (Arctic fox, Vulpes lagopus). We describe a number of confounding variables that must be addressed when conducting toxicogenomics studies in canid and other mammalian models. The ability for canids to act as models for Arctic molecular toxicology research is unique and significant for advancing our understanding and expanding the tool box for assessing the changing landscape of environmental agents of disease in the Arctic.

Figure 1

Boundary of the Arctic Monitoring and Assessment Program (AMAP) that will be considered as the delineation for the “Arctic” region in this study. Figure from AMAP (2009).

Figure 2

Hypothetical up-regulation (a) and down-regulation (b) profiles for genes expressed over time in response to environmental contaminants. By sampling at time 0 (baseline) and comparing the expression of these genes to post-treatment time points (time 1–3), we determined that it is clear that some gene response and time points will result in variable ability to detect biological response (c).

Figure 3

Concentrations of THg in WB measured in sled dogs fed 50% fish and 50% kibble (fish group, n = 4) and 100% kibble (kibble group, n = 4). THg values for the kibble group were below detection limit for all weeks sampled. Data from Lieske et al.

Figure 4

(a) MT2A expression at Week 11 (fold-change from Week 0) was determined to be significantly different between treatment groups. Error bars represent standard error (b). However, some dogs showed large variability in MT2A expression (log₂ fold-change) for Week n compared to Week 0 over the course of the feeding trial. Here, the gray lines represent the mean for each treatment group per week. Each colored line represents an individual animal. We emphasize that single-time point analysis of gene response might not reflect variability found in in vivo studies.

Figure 5

(a) Log₂ expression of GSTP1 was positively associated with the percent lymphocytes in the whole blood sample, and (b) log₂ GPX1 expression was positively correlated with weight of the animal (kg) (p < 0.01).