Control of thymocyte development and recombination-activating gene expression by the zinc finger protein Zfp608.

Zhang F, Thomas LR, Oltz EM, Aune TM
Nat Immunol. 2006 7 (12): 1309-16

PMID: 17057722 · DOI:10.1038/ni1397

The products of recombination-activating gene 1 (Rag1) and Rag2 are required for T cell receptor gene assembly and thymocyte maturation, yet their transcriptional control mechanisms remain unclear. A congenic strain (called 'ZORI' here) with defects in Rag1 and Rag2 expression, thymocyte maturation and peripheral T cell homeostasis has been developed. Here, we mapped the mutation in this strain to a chromosome 18 locus containing a single known gene encoding the zinc finger protein Zfp608. This gene (Zfp608) was highly expressed in neonatal thymus but was extinguished thereafter. In contrast to wild-type mice, ZORI mice had sustained thymocyte expression of Zfp608 throughout life. The ZORI mutation produced a thymocyte-intrinsic developmental defect. Overexpression of Zfp608 in BALB/c thymocytes substantially impaired Rag1 and Rag2 expression, indicating the underlying mechanism for the defect in ZORI thymocyte development. Thus, the normal function of Zfp608 may be to prevent Rag1 and Rag2 expression in utero.

MeSH Terms (14)

Animals DNA-Binding Proteins Flow Cytometry Gene Expression Genes, RAG-1 Immunoblotting In Situ Hybridization Lymphocytes Mice Mice, Congenic Mutation Reverse Transcriptase Polymerase Chain Reaction Thymus Gland Zinc Fingers

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