Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice.

Détails

ID Serval
serval:BIB_8DC81DF45098
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice.
Périodique
Molecular and Cellular Biology
Auteur(s)
Yang Z.Z., Tschopp O., Di-Poï N., Bruder E., Baudry A., Dümmler B., Wahli W., Hemmings B.A.
ISSN
0270-7306[print], 0270-7306[linking]
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
25
Numéro
23
Pages
10407-10418
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, Animals, Newborn, Cardiovascular System/embryology, Cardiovascular System/enzymology, Cells, Cultured, Embryo Loss, Embryo, Mammalian/abnormalities, Embryo, Mammalian/embryology, Embryonic Development, Female, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Isoenzymes/deficiency, Isoenzymes/genetics, Male, Mice, Mice, Knockout, Mutation/genetics, Neurons/enzymology, Organ Specificity, Proto-Oncogene Proteins c-akt/deficiency, Proto-Oncogene Proteins c-akt/genetics, Skin/embryology, Skin/enzymology, Survival Rate, Thymus Gland/embryology, Thymus Gland/enzymology
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 17:05
Dernière modification de la notice
08/05/2019 21:50
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