TY - JOUR
T1 - Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the ikaros transcription factor
AU - Papathanasiou, Peter
AU - Perkins, Andrew C.
AU - Cobb, Bradley S.
AU - Ferrini, Roger
AU - Sridharan, Rupa
AU - Hoyne, Gerard F.
AU - Nelms, Keats A.
AU - Smale, Stephen T.
AU - Goodnow, Christopher C.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - A central issue in understanding the hematolymphoid system is the generation of appropriate mutant alleles in mice to reveal the function of regulatory genes. Here we describe a mouse strain, Plastic, with a point mutation in a zinc finger of Ikaros that disrupts DNA binding but preserves efficient assembly of the full-length protein into higher order complexes. IkarosPlastic homozygosity is embryonically lethal with severe defects in terminal erythrocyte and granulocyte differentiation, excessive macrophage formation, and blocked lymphopoiesis, while heterozygotes display a partial block in lymphocyte differentiation. The contrast with more circumscribed effects of Ikaros alleles that ablate the full-length protein highlights the importance in mammals of generating recessive niche-filling alleles that inactivate function without creating a void in multimolecular assemblies.
AB - A central issue in understanding the hematolymphoid system is the generation of appropriate mutant alleles in mice to reveal the function of regulatory genes. Here we describe a mouse strain, Plastic, with a point mutation in a zinc finger of Ikaros that disrupts DNA binding but preserves efficient assembly of the full-length protein into higher order complexes. IkarosPlastic homozygosity is embryonically lethal with severe defects in terminal erythrocyte and granulocyte differentiation, excessive macrophage formation, and blocked lymphopoiesis, while heterozygotes display a partial block in lymphocyte differentiation. The contrast with more circumscribed effects of Ikaros alleles that ablate the full-length protein highlights the importance in mammals of generating recessive niche-filling alleles that inactivate function without creating a void in multimolecular assemblies.
UR - http://www.scopus.com/inward/record.url?scp=0038106526&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(03)00168-7
DO - 10.1016/S1074-7613(03)00168-7
M3 - Article
SN - 1074-7613
VL - 19
SP - 131
EP - 144
JO - Immunity
JF - Immunity
IS - 1
ER -