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. Author summary Pw1/Peg3 is under parental specific epigenetic regulation. We propose that Pw1/Peg3 confers a selective advantage in mammals by regulating sexual dimorphism. To address this question, we examined the consequences of Pw1/Peg3 loss of function in mice in an age- and sex-dependent context and found that Pw1/Peg3 mutants display reduced sexual dimorphism in growth, metabolism and behaviors. Our findings support the intralocus sexual conflict model of genomic imprinting where it contributes in sexual differentiation. Furthermore, our observations provide a unifying role of sex steroid signaling as a common property of Pw1/Peg3 expressing stem/progenitor cells and differentiated endocrine cells, both of which remain proliferative in response to gonadal hormones in adult life.
【초록키워드】 Sex, metabolism, Brain, Adiposity, Characteristics, cells, mice, insulin resistance, male, female, pathway, sexual dimorphism, age, hormone, Behavior, Fatty liver, mutant, genomic, insulin, Epigenetic, Signaling, Endocrine, steroid, life, genomic imprinting, Support, observation, Diabetic, Regulation, sex steroid, postnatal development, tissues, growth, alteration, adulthood, allele, phenotypic, mammals, selective, weaning, Peg3, puberty, Cell, consequence, loss of function, develop, examined, reduced, provide, question, contribute, expressed, promote, expressing, manifested, parental, accelerated, proliferative, mammal, fat accumulation, gonadal, masculinization, 【제목키워드】 expressed, promote,