Deletion of PKBalpha/Akt1 affects thymic development.
BACKGROUND
The thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway.


RESULTS
To determine whether PKB mediates PI3K signaling in the thymus, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha(-/-) neonates and an accumulation of early thymocyte subsets in PKBalpha(-/-) adult mice. Using thymic grafting and fetal liver cell transfer experiments, the latter finding was specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals.


CONCLUSIONS
This report highlights the specific requirements of PKBalpha for thymic development and opens up new prospects as to the mechanism downstream of PKBalpha in early thymocytes.
Fayard
Elisabeth
E
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Gill
Jason
J
Paolino
Magdalena
M
Hynx
Debby
D
Holländer
Georg A
GA
Hemmings
Brian A
BA
D000818:Animals; D000831:Animals, Newborn; D002469:Cell Separation; D017690:Cell Transplantation / Q000379:methods; D017353:Gene Deletion; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt