Essential role of protein kinase B gamma (PKB gamma/Akt3) in postnatal brain development but not in glucose homeostasis.
Protein kinase B is implicated in many crucial cellular processes, such as metabolism, apoptosis and cell proliferation. In contrast to Pkb(alpha) and Pkb(beta)-deficient mice, Pkb(gamma)(-/-) mice are viable, show no growth retardation and display normal glucose metabolism. However, in adult Pkb(gamma)mutant mice, brain size and weight are dramatically reduced by about 25%. In vivo magnetic resonance imaging confirmed the reduction of Pkb(gamma)(-/-) 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 Pkb(gamma)(-/-) 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 Pkb(gamma) and suggest a crucial role in postnatal brain development.
Tschopp
Oliver
O
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Yang
Zhong-Zhou
ZZ
Brodbeck
Daniela
D
Dummler
Bettina A
BA
Hemmings-Mieszczak
Maja
M
Watanabe
Takashi
T
Michaelis
Thomas
T
Frahm
Jens
J
Hemmings
Brian A
BA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D002452:Cell Count; D005298:Fertility / Q000235:genetics; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000235:genetics
D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose