The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding.
Genomic imprinting, by which maternal and paternal alleles of some genes have different levels of activity, has profound effects on growth and development of the mammalian fetus. The action of imprinted genes after birth, in particular while the infant is dependent on maternal provision of nutrients, is far less well understood. We disrupted a paternally expressed transcript at the Gnas locus, Gnasxl, which encodes the unusual Gs alpha isoform XL alpha s. Mice with mutations in Gnasxl have poor postnatal growth and survival and a spectrum of phenotypic effects that indicate that XL alpha s controls a number of key postnatal physiological adaptations, including suckling, blood glucose and energy homeostasis. Increased cAMP levels in brown adipose tissue of Gnasxl mutants and phenotypic comparison with Gnas mutants suggest that XL alpha s can antagonize Gs alpha-dependent signaling pathways. The opposing effects of maternally and paternally expressed products of the Gnas locus provide tangible molecular support for the parental-conflict hypothesis of imprinting.
Plagge
Antonius
A
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, CB2 4AT, UK.
Gordon
Emma
E
Dean
Wendy
W
Boiani
Romina
R
Cinti
Saverio
S
Peters
Jo
J
Kelsey
Gavin
G
D000273:Adipose Tissue; D000818:Animals; D001921:Brain / Q000378:metabolism; D002864:Chromogranins; D004734:Energy Metabolism / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D005804:Genes, Lethal; D018392:Genomic Imprinting; D006128:Growth / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D015398:Signal Transduction; D013391:Sucking Behavior
D002864:Chromogranins; C498642:Gnas protein, mouse; D019205:GTP-Binding Protein alpha Subunits, Gs