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

Karo Tanaka (1) , Vanessa Besson (1) , Manon Rivagorda (2) , Franck Oury (2) , Giovanna Marazzi (1) , David A. Sassoon (1)

1 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
2 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades

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.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Biologie du développement

Karo Tanaka, Vanessa Besson, Manon Rivagorda, Franck Oury, Giovanna Marazzi, et al.. Paternally expressed gene 3 (Pw1/Peg3) promotes sexual dimorphism in metabolism and behavior. PLoS Genetics, 2022, 18 (1), pp.e1010003. ⟨10.1371/journal.pgen.1010003⟩. ⟨hal-03531481⟩