Life with a Single Isoform of Akt: Mice Lacking Akt2 and Akt3 Are Viable but Display Impaired Glucose Homeostasis and Growth Deficiencies

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Aug 23

PMID 16923958

Citations 134

Authors

Bettina Dummler

Oliver Tschopp

Debby Hynx

Zhong-Zhou Yang

Stephan Dirnhofer

Brian A Hemmings

Affiliations

Soon will be listed here.

Abstract

To address the issues 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 an approximately 25% reduction in body weight compared to wild-type mice. In addition, we found substantial reductions in relative size and weight of the 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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