Reciprocal F1 Hybrids of Two Inbred Mouse Strains Reveal Parent-of-Origin and Perinatal Diet Effects on Behavior and Expression

G3 : Genes - Genomes - Genetics
D OreperL M Tarantino

Abstract

Parent-of-origin effects (POE) in mammals typically arise from maternal effects or imprinting. In some instances, such POE have been associated with psychiatric disorders, as well as with changes in a handful of animal behaviors. However, POE on complex traits such as behavior remain largely uncharacterized. Moreover, although both behavior and epigenetic effects are known to be modified by perinatal environmental exposures such as nutrient deficiency, the architecture of such environment-by-POE is mostly unexplored. To study POE and environment-by-POE, we employ a relatively neglected but especially powerful experimental system for POE-detection: reciprocal F1 hybrids (RF1s). We exposed female NOD/ShiLtJ×C57Bl/6J and C57Bl/6J×NOD/ShiLtJ mice, perinatally, to one of four different diets, then after weaning recorded a set of behaviors that model psychiatric disease. Whole-brain microarray expression data revealed an imprinting-enriched set of 15 genes subject to POE. The most-significant expression POE, on the non-imprinted gene Carmil1 (a.k.a. Lrrc16a), was validated using qPCR in the same and in a new set of mice. Several behaviors, especially locomotor behaviors, also showed POE. Bayesian mediation analysis suggested Carmil1 ...Continue Reading

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Methods Mentioned

BETA
PCR
GTPase

Software Mentioned

Affymetrix
TargetScan
R
R package nlme
Activity Monitor
lme4
Actimetrics Freeze Frame
miRHub
ABI CopyCaller
lmerTest

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