Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the ikaros transcription factor

Peter Papathanasiou, Andrew C. Perkins, Bradley S. Cobb, Roger Ferrini, Rupa Sridharan, Gerard F. Hoyne, Keats A. Nelms, Stephen T. Smale, Christopher C. Goodnow

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112 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)131-144
Number of pages14
JournalImmunity
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Jul 2003

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