Essential role of protein kinase Bγ (PKBγ/Akt3) in postnatal brain development but not in glucose homeostasis
Author:
Tschopp Oliver1, Yang Zhong-Zhou1, Brodbeck Daniela1, Dummler Bettina A.1, Hemmings-Mieszczak Maja2, Watanabe Takashi3, Michaelis Thomas3, Frahm Jens3, Hemmings Brian A.1
Affiliation:
1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66,CH-4058 Basel, Switzerland 2. Novartis Pharma AG, Lichtstrasse 35, CH-4056, Basel, Switzerland 3. Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37070 Göttingen, Germany
Abstract
Protein kinase B is implicated in many crucial cellular processes, such as metabolism, apoptosis and cell proliferation. In contrast to Pkbα and Pkbβ-deficient mice, Pkbγ-/- mice are viable, show no growth retardation and display normal glucose metabolism. However, in adult Pkbγmutant mice, brain size and weight are dramatically reduced by about 25%. In vivo magnetic resonance imaging confirmed the reduction of Pkbγ-/- brain volumes with a proportionally smaller ventricular system. Examination of the major brain structures revealed no anatomical malformations except for a pronounced thinning of white matter fibre connections in the corpus callosum. The reduction in brain weight of Pkbγ-/- mice is caused, at least partially, by a significant reduction in both cell size and cell number. Our results provide novel insights into the physiological role of PKBγ and suggest a crucial role in postnatal brain development.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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