Regulation of Maternal Behavior and Offspring Growth by Paternally Expressed Peg3

Abstract

Imprinted genes display parent-of-origin-dependent monoallelic expression that apparently regulates complex mammalian traits, including growth and behavior. The Peg3 gene is expressed in embryos and the adult brain from the paternal allele only. A mutation in the Peg3 gene resulted in growth retardation, as well as a striking impairment of maternal behavior that frequently resulted in death of the offspring. This result may be partly due to defective neuronal connectivity, as well as reduced oxytocin neurons in the hypothalamus, because mutant mothers were deficient in milk ejection. This study provides further insights on the evolution of epigenetic regulation of imprinted gene dosage in modulating mammalian growth and behavior.

Reprogramming of genome function through epigenetic inheritance

“…Imprinted genes may regulate some of the crucial aspects of mammalian physiology associated with reproduction, placentation, energy homeostasis, lactation and behaviour [16][17][18] . For example, Igf2, which encodes a fetal insulin-like growth factor 2, is repressed in the maternal genome and active only in the paternal genome 19 .…”

Genomic imprinting and mammalian reproduction

“…Li et al (1999) noted very high levels of pre-weaning mortality in the offspring 201" of heterozygous Peg3 mutant females despite these pups being wild-type, having been 202" fathered by wild-type males with normal Peg3 expression. The elevated mortality thus could 203" not have been due to direct genetic effects in the wild-type offspring but rather to the 204" maternal responses of the females.…”

“…The Peg3 mutation also affects thermoregulation as mutant pups are unable to 169" maintain body temperature in response to maternal separation. Metabolism, appetite and 170" thermoregulation are all mediated by the hypothalamus, an area where there is high Peg3 171" expression during development (Li et al, 1999). The Peg3 protein is involved in p53-172" mediated apoptosis (Deng and Wu, 2000) and these mutant animals show alterations in 173" postnatal hypothalamic apoptosis (Broad et al, 2009), which suggests that aberrant 174" neuronal pruning during development may disrupt normal functioning of the hypothalamus.…”

Early experience and parent-of-origin-specific effects influence female reproductive success in mice

“…We created males and females of reciprocal genotype using mice of the B6 (C57Bl/6) and CBA (CBA/Ca) strains, which are an ideal model system to study fitness consequences of parent-of-originspecific effects because they differ consistently in key life-history parameters such as litter size (Hager & Johnstone 2003) and inbred mice have been extensively used in research on genomic imprinting (Li et al 1999). The general features of these strains and their breeding have been described elsewhere (Hager & Johnstone 2003, 2005.…”

“…Parent-of-origin-specific effects such as genomic imprinting have been shown to significantly affect measures of fitness in mammals (Li et al 1999). Their evolution is thought to be the result of differential fitness effects in males and females and stems from a conflict between the sexes over the optimal level of maternal investment (Haig 2004).…”