Paternally expressed gene 3 (Pw1/Peg3) promotes sexual dimorphism in metabolism and behavior.

Karo Tanaka,David A Sassoon,Franck Oury,Manon Rivagorda,Giovanna Marazzi,Vanessa Besson,Rebecca J Oakey

doi:10.1371/journal.pgen.1010003

Abstract

The paternally expressed gene 3 (Pw1/Peg3) is a mammalian-specific parentally imprinted gene expressed in stem/progenitor cells of the brain and endocrine tissues. Here, we compared phenotypic characteristics in Pw1/Peg3 deficient male and female mice. Our findings indicate that Pw1/Peg3 is a key player for the determination of sexual dimorphism in metabolism and behavior. Mice carrying a paternally inherited Pw1/Peg3 mutant allele manifested postnatal deficits in GH/IGF dependent growth before weaning, sex steroid dependent masculinization during puberty, and insulin dependent fat accumulation in adulthood. As a result, Pw1/Peg3 deficient mice develop a sex-dependent global shift of body metabolism towards accelerated adiposity, diabetic-like insulin resistance, and fatty liver. Furthermore, Pw1/Peg3 deficient males displayed reduced social dominance and competitiveness concomitant with alterations in the vasopressinergic architecture in the brain. This study demonstrates that Pw1/Peg3 provides an epigenetic context that promotes male-specific characteristics through sex steroid pathways during postnatal development.

Highlights

Parental genomic imprinting is a form of epigenetic regulation by which one allele of a gene is expressed according to its parent-of-origin
We propose that Pw1/Peg3 confers a selective advantage in mammals by regulating sexual dimorphism
We examined the consequences of Pw1/Peg3 loss of function in mice in an ageand sex-dependent context and found that Pw1/Peg3 mutants display reduced sexual dimorphism in growth, metabolism and behaviors

Summary

Introduction

Parental genomic imprinting is a form of epigenetic regulation by which one allele of a gene is expressed according to its parent-of-origin. In vertebrates, this form of imprinting is unique to placental mammals and its evolutionary advantage is still under active debate [1,2,3]. Day and Bonduriansky proposed an ‘intralocus sexual conflict’ model [6] that predicts a physiological role for genomic imprinting in the genetic architecture of sexually dimorphic traits. This hypothesis is applicable to any species and traits under sex-specific selection pressure. Empirical exploration of the role of imprinted genes in sexual differentiation is relatively limited [7,8]

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Conclusion