Ml. Carrozza et al., OVEREXPRESSION OF THE FOSB2 GENE IN THYMOCYTES CAUSES ABERRANT DEVELOPMENT OF T-CELLS AND THYMIC EPITHELIAL-CELLS, Oncogene, 14(9), 1997, pp. 1083-1091
We have examined the role of the AP-1 transcription factor on thymocyt
e maturation and thymus architecture by overexpressing FosB2 in transg
enic mice. FosB2 is a naturally occurring splice variant of the FosB2
gene, encoding a truncated protein which lacks two domains necessary f
or transcriptional activation. The expression of FosB2 in the thymocyt
es severely affected their maturation and the structure of the whole t
hymus: the phenotype developed slowly during the first months of life,
resulting in a progressive expansion of the medulla and concomitant r
eduction of the cortex. CD4(+) thymocytes represented the major thymoc
yte population, whereas the CD4(+)8(+) thymocytes were virtually absen
t. This phenotype appeared to be an intrinsic property of bone marrow
derived cells, as it could be reproduced in bone marrow chimaeric mice
, This pathology was very reminiscent to that observed in mice overexp
ressing c-Fos in thymic epithelium: also in that case the thymus under
went with age a progressive expansion of the epithelium and major chan
ges in the ratio of thymocyte subsets, but the phenotype appeared to b
e an intrinsic property of the epithelial cells since it could not be
reproduced by transgenic bone marrow transplantation. We speculate tha
t both overexpression of FosB2 in thymocytes and overexpression of c-F
os in thymic epithelium results in aberrant signaling between thymocyt
es and stroma, that ultimately alters the thymic micromilieu, leading
to this severe pathology.