What’s mainly orange, sometimes a little black, and usually obese? Congratulations if you guessed Agouti (Avy) mice! (And you may want to consider spending less time in a vivarium) These chubby little creatures are well established as environmental epigenetics models because a number of environmental exposures are known to alter DNA methylation at the Avy locus. New research details how lead (Pb) exposure effects the Agouti epigenome.
How DNA methylation alters the Agouti phenotype
Dr. Chris Faulk and his colleagues at University of Michigan’s NIH/EPA funded Children’s Environmental Health Center noticed that “most of the previous studies used dietary supplements that can directly affect the 1-carbon metabolism pathway, or are endocrine disruptors, such as BPA.” And saw the need to distinguish between direct and indirect environmental epigenetic effects. Here’s what they found:
- “Lead (Pb) exposure can also alter the DNA methylation, despite not interacting directly with the 1-carbon metabolism pathway.:
- “Two types of loci often used to detect environmental perturbations, transposon insertions and imprinted genes, react differently to lead exposure.” This suggested that “locus-specific effects may serve as signatures of historical exposures”.
- “The shifts in phenotype as measured by an increasing distribution of animals with yellow fur, and increasing wean weight, correlated with increased levels of lead exposure.”
- “However, the DNA methylation shift at the two transposon insertions, Avy and CabpIAP, did not follow a linear increase as we expected, but instead showed cubic trends. These significant trends indicate that lead acts in a non-monotonic fashion.”
Faulk and crew were somewhat surprised that “the largest increase as compared to control DNA methylation levels occurred at the lowest exposure, well within blood lead levels in humans frequently observed in humans.” He also elaborates that the “Epigenetic effects appear to be specific to some classes of genes while having a lesser effect on others. Similarly, sex-specific effects may enhance or mediate the resulting phenotypic changes induced by lead and should be measured separately in follow-up mouse and human studies.”
Faulk concludes with his concerns that “Lead is a persistent environmental toxicant with significant effects even at blood levels consistent with the lowest CDC recommended action threshold. Moreover, the epigenetic effects established in early development may last long beyond the initial exposure event.”
Get the lead out of your head over at Epigenomics, October 2013