title: Akt1 and insulin-like growth factor 2 (Igf2) regulate placentation and fetal/postnatal development.
abstract: Phenotypic characterization of Akt1 and Igf2 null mice has revealed roles for each in the regulation of placentation, and fetal and postnatal growth. Insulin-like growth factor 2 (IGF2) is encoded by the Igf2 gene and influences cellular function, at least in part, through activation of an intracellular serine/threonine kinase called AKT1. Akt1 and Igf2 null mice were originally characterized on inbred and mixed genetic backgrounds, prohibiting direct comparisons of their phenotypes. The impact of loss of AKT1 or IGF2 on placental, fetal, and postnatal function were examined following transfer of Akt1 and Igf2 null mutations to an outbred CD1 genetic background. Disruption of IGF2 did not affect AKT expression or activation. Both Akt1-/- and Igf2-/- mice exhibited decreased placental weight, fetal weight and viability. Deregulation of placental growth was similar in Akt1 and Igf2 nulls; however, disruption of Igf2 had a more severe impact on prenatal survival and postnatal growth. Placental structure, including organization of junctional and labyrinth zones and development of the interstitial, invasive, trophoblast lineage, were similar in mutant and wild-type mice. Akt1 and Igf2 null mutations affected postnatal growth. The relative impact of each gene differed during pre-weaning versus post-weaning growth phases. AKT1 had a more significant role during pre-weaning growth, whereas IGF2 was a bigger contributor to post-weaning growth. Akt1 and Igf2 null mutations impact placental, fetal and postnatal growth. Placental phenotypes are similar; however, fetal and postnatal growth patterns are unique to each mutation.
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Kent
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohboshi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Soares
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology*; D005328:Fetal Viability / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010920:Placenta / Q000378:metabolism; D010929:Placentation / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D014886:Weaning
chemical_list: C513121:IGF2 protein, mouse; D007335:Insulin-Like Growth Factor II; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt