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Abstract
<p class="first" id="P2">The Ikaros family of transcription factors includes five
highly homologous members
that can homodimerize or heterodimerize in any combination. Dimerization is essential
for their ability to bind DNA and function as transcription factors. Previous studies
showed that eliminating the function of the entire family blocks lymphocyte development
while deletion of individual family members has relatively minor defects. These data
indicate that multiple family members function during T cell development, so we examined
the changes in expression of each family member as thymocytes progressed from the
CD4
<sup>−</sup>CD8
<sup>−</sup> double negative (DN) to the CD4
<sup>+</sup>CD8
<sup>+</sup> double positive (DP) developmental stage. Further, we compared the expression
of
each family member in murine and human thymocytes. In both species, Ikaros and Aiolos
mRNA levels increased as thymocytes progressed through the DN to DP transition, but
the corresponding increases in protein levels were only observed in mice. Further,
Ikaros and Aiolos underwent extensive alternative splicing in mice, whereas only Ikaros
was extensively spliced in humans. Helios mRNA and protein levels decreased during
murine T cell development, but increased during human T cell development. These differences
in the expression and splicing of Ikaros family members between human and murine thymocytes
strongly suggest that the Ikaros family of transcription factors regulates murine
and human T cell development differently, although the similarities across Ikaros
family members may allow different proteins to fulfill similar functions.
</p>