[PDF][PDF] Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation

JH Wang, A Nichogiannopoulou, L Wu, L Sun… - Immunity, 1996 - cell.com
JH Wang, A Nichogiannopoulou, L Wu, L Sun, AH Sharpe, M Bigby, K Georgopoulos
Immunity, 1996cell.com
Mice homozygous for an Ikaros null mutation display distinct defects in the development of
fetal and adult lymphocytes. Fetal T lymphocytes, and fetal and adult B lymphocytes and
their earliest progenitors are absent. Postnatally, hematopoietic stem cells give rise to
thymocyte precursors that undergo aberrant differentiation into the CD4 lineage and clonal
expansion. The lack of NK cells and some γδ T cell subsets and a large reduction in thymic
dendritic APCs suggest that Ikaros is essential for establishing early branch points in the …
Abstract
Mice homozygous for an Ikaros null mutation display distinct defects in the development of fetal and adult lymphocytes. Fetal T lymphocytes, and fetal and adult B lymphocytes and their earliest progenitors are absent. Postnatally, hematopoietic stem cells give rise to thymocyte precursors that undergo aberrant differentiation into the CD4 lineage and clonal expansion. The lack of NK cells and some γδ T cell subsets and a large reduction in thymic dendritic APCs suggest that Ikaros is essential for establishing early branch points in the postnatal T cell pathway. The lymphoid defects detected in Ikaros null mice reveal critical molecular differences between fetal and postnatal hematopoietic progenitors that dictate their ability to give rise to T cells. These studies also establish Ikaros as a tumor suppressor gene acting during thymocyte differentiation. Phenotypic comparison of this null mutation with a severe dominant-negative Ikaros mutation identifies molecular redundancy in the postnatal hemolymphoid system.
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