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Abstract #0797

MR Imaging Detects Impaired Angiogenesis and Trabecular Bone Formation During Endochondral Bone Growth Mediated Through PKBalpha/Akt1 in Gene Dosage Dependent Manner

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.