Essential role of protein kinase Bγ (PKBγ/Akt3) in postnatal brain development but not in glucose homeostasis

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 Pkbγ mutant 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.