title: Pleiotropic effects of a methyl donor diet in a novel animal model.
abstract: Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent prenatal neural tube defects. Several lines of evidence suggest that these supplements act through epigenetic mechanisms (e.g. altering DNA methylation). Primary among these are the experiments on the mouse viable yellow allele of the agouti locus (A(vy)). In the Avy allele, an Intracisternal A-particle retroelement has inserted into the genome adjacent to the agouti gene and is preferentially methylated. To further test these effects, we tested the same diet used in the Avy studies on wild-derived Peromyscus maniculatus, a native North American rodent. We collected tissues from neonatal offspring whose parents were fed the high-methyl donor diet as well as controls. In addition, we assayed coat-color of a natural variant (wide-band agouti = A(Nb)) that overexpresses agouti as a phenotypic biomarker. Our data indicate that these dietary components affected agouti protein production, despite the lack of a retroelement at this locus. Surprisingly, the methyl-donor diet was associated with defects (e.g. ovarian cysts, cataracts) and increased mortality. We also assessed the effects of the diet on behavior: We scored animals in open field and social interaction tests. We observed significant increases in female repetitive behaviors. Thus these data add to a growing number of studies that suggest that these ubiquitously added nutrients may be a human health concern.
authors.affiliation: Peromyscus Genetic Stock Center University of South Carolina, Columbia, South Carolina, United States of America; Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Shorter
authors.affiliation: Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Anderson
authors.affiliation: Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cakora
authors.affiliation: Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Owen
authors.affiliation: Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Keswick
authors.initials: K
authors.lastname: Lo
authors.affiliation: Peromyscus Genetic Stock Center University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Janet
authors.initials: J
authors.lastname: Crossland
authors.affiliation: Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: April C H
authors.initials: AC
authors.lastname: South
authors.affiliation: Peromyscus Genetic Stock Center University of South Carolina, Columbia, South Carolina, United States of America; Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Felder
authors.affiliation: Peromyscus Genetic Stock Center University of South Carolina, Columbia, South Carolina, United States of America; Dept. Biological Sciences, University of South Carolina, Columbia, South Carolina, United States of America.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Vrana
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D004032:Diet; D006200:Hair Color; D023421:Models, Animal; D009436:Neural Tube Defects / Q000517:prevention & control*; D010542:Peromyscus