Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation.
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 gamma delta 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.
Wang
J H
JH
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
Nichogiannopoulou
A
A
Wu
L
L
Sun
L
L
Sharpe
A H
AH
Bigby
M
M
Georgopoulos
K
K
D000818:Animals; D001853:Bone Marrow / Q000196:embryology / Q000254:growth & development; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002999:Clone Cells; D004268:DNA-Binding Proteins; D003713:Dendritic Cells; D004920:Erythropoiesis; D005091:Exons / Q000235:genetics; D051740:Ikaros Transcription Factor; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D008213:Lymphocyte Activation; D008214:Lymphocytes; D008221:Lymphoid Tissue / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D014176:Protein Biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D017384:Sequence Deletion; D013154:Spleen / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D016176:T-Lymphocyte Subsets; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics*
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor