title: Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice.
abstract: Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1-/- Akt3+/- mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1+/- Akt3-/- mice survive normally. Double knockout (Akt1-/-) Akt3-/-) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specific and dosage-dependent effects of Akt on animal survival and development.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, Maulbeerstrasse 66, Basel CH-4002, Switzerland.
authors.forename: Zhong-Zhou
authors.initials: ZZ
authors.lastname: Yang
authors.forename: Oliver
authors.initials: O
authors.lastname: Tschopp
authors.forename: Nicolas
authors.initials: N
authors.lastname: Di-Poï
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bruder
authors.forename: Anne
authors.initials: A
authors.lastname: Baudry
authors.forename: Bettina
authors.initials: B
authors.lastname: Dümmler
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
authors.forename: Brian A
authors.initials: BA
authors.lastname: Hemmings
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002319:Cardiovascular System / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D002478:Cells, Cultured; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000196:embryology / Q000201:enzymology; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D009928:Organ Specificity; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D015996:Survival Rate; D013950:Thymus Gland / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development
chemical_list: D007527:Isoenzymes; D051057:Proto-Oncogene Proteins c-akt