PMID: 11900414Mar 20, 2002Paper

A transgenic mouse strain with antigen-specific T cells (RAG1KO/sf/OVA) demonstrates that the scurfy (sf) mutation causes a defect in T-cell tolerization

Comparative Medicine
J L Zahorsky-Reeves, J E Wilkinson

Abstract

The scurfy (sf) murine mutation causes severe lymphoproliferation, which results in death of hemizygous males (sf/Y) by 22 to 26 days of age. The CD4+ T cells are crucial mediators of this disease. Recent publications have not only identified this mutation as the genetic equivalent of the human disease X-linked neonatal diabetes mellitus, enteropathy, and endocrinopathy syndrome, but also have indicated that the defective protein-scurfin-is a new forkhead/winged-helix protein with a frameshift mutation, resulting in a product without the functional forkhead. These results have lead to speculation that the scurfy gene acts by disrupting the T-cell tolerance mechanism, resulting in hyperresponsiveness and lack of down-regulation. The Rag1KO/sf/Y OVA strain, with virtually 100% of its CD4+ T cells reactive strictly to ovalbumin (OVA) peptide 323-339, is an excellent model for determination of the sf mutation's ability to disrupt tolerance. We hypothesized that Rag1KO/sf/OVA mice would not be tolerant to antigen at a dose that tolerizes control animals. We found that splenic cells from Rag1KO/sf/Y OVA mice injected with the same dose of OVA peptide that induces tolerance in cells from control mice proliferate in vitro in response t...Continue Reading

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