Foxp3DTR knock-in mice contain an internal ribosome entry site (IRES), a human diphtheria toxin receptor (DTR), and an enhanced green fluorescent protein (EGFP) downstream of the internal stop codon of the X-linked forkhead box P3 (Foxp3) gene. FOXP3 is a transcription factor required for the development and function of regulatory T (T reg) cells, which are required for suppression of self-reactive T cells and prevention of some autoimmune diseases. In these mice, DTR-EGFP expression is evident in FOXP3+ Treg cells. Diphtheria toxin (DT) administration results in ablation of Treg cells in thymus, lymph nodes, and spleen 2 days after injection, with cell numbers rebounding 10-15 days post-injection. Neonates injected with DT daily all die from lymphoproliferative disease, indicated by failure to thrive, lack of mobility, ventral skin lesions, hunched posture, and conjunctivitis, within 27 days of birth. With the same DT treatment, adults exhibit a more rapid development of autoimmune disease and die within 3 weeks. These mice show an increase in CD4+ T cell activation, as well as an increase in the number of B cells, macrophages, granulocytes, natural killer, and dendritic cells in the spleen and lymph nodes. Homozygous females and hemizygous males are viable, fertile, and normal in size. These mice may be useful for visualizing and specifically eliminating regulatory T cells, and for studying autoimmunity and immune dysfunction.
