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Mol. Cell. Biol. doi:10.1128/MCB.00722-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Life with a single isoform of Akt: Mice lacking Akt2 and Akt3 are viable but display affected glucose homeostasis and growth deficiencies

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, Basel, CH-4058, Switzerland; Institute of Pathology, University of Basel, Schönbeinstrasse 40, Basel, CH-4031, Switzerland

^* To whom correspondence should be addressed. Email: brian.hemmings{at}fmi.ch.

	Abstract

To address the question of isoform-redundancy and isoform-specificity of the Akt family of protein kinases in vivo, we generated mice deficient in both Akt2 and Akt3. In these mice only the Akt1 isoform remains to perform essential Akt functions, such as glucose homeostasis, proliferation, differentiation, and early development. Surprisingly, we found that Akt2^-/-Akt3^-/- and even Akt1^+/-Akt2^-/-Akt3^-/- mice developed normally and survived with minimal dysfunctions despite a dramatic reduction of total Akt levels in all tissues. A single functional allele of Akt1 appears to be sufficient for successful embryonic development and postnatal survival. This is in sharp contrast to the previously described lethal phenotypes of Akt1^-/-Akt2^-/- mice and Akt1^-/-Akt3^-/- mice. However, Akt2^-/-Akt3^-/- mice were glucose and insulin intolerant and exhibited a 25% reduction in body weights compared to wild type mice. In addition, we found a substantial reduction in relative size and weight of brain and testis in Akt2^-/-Akt3^-/- mice, demonstrating an in vivo role for both Akt2 and Akt3 in the determination of whole animal size and individual organ sizes.

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