Katrien Vandoorne1, Jeremy Magland2,
Vicki Plaks1, Inbal E. Biton3, Amnon Sharir4,5,
Elazar Zelzer4, Felix Wehrli6, Brian A. Hemmings7,
Alon Harmelin3, Michal Neeman1
1Biological Regulation, Weizmann
Institute, Rehovot, Israel; 2Department of Radiology, University
of Pennsylvania Health System, Philadelphia, PA, United States; 3Veterinary
Resources, Weizmann Institute, Rehovot, Israel; 4Molecular
Genetics, Weizmann Institute, Rehovot, Israel; 5The Laboratory of
Musculoskeletal Biomechanics and Applied Anatomy, Koret School of Veterinary
Medi, Hebrew University of Jerusalem, Rehovot, Israel; 6Department
of Radiology, University of Pennsylvania Health System, Philadelphia, PA,
Israel; 7Friedrich Miescher Institute for Biomedical Research,
Basel, Switzerland
Since
infiltration of the newly formed blood vessels is required for endochondral
bone formation, and PKBalpha/Akt1 mediates intracellular signaling of
angiogenesis, we postulated that a vascular deficiency at the site of the
long bones could contribute indirectly to impaired bone development in
PKBalpha/Akt1 deficient mice. Our study demonstrated using macromolecular
DCE-MRI in vivo and ex vivo CT and MRI, vascular and bone developmental
defects in PKBalpha/Akt1 null mice, and remarkably also in heterozygous mice,
lacking a single copy of the gene.