T-box proteins are characterized by having a T-domain, which is a highly conserved DNA-binding region of about 200 amino acids. The T-box proteins are expressed during embryo development and play an important role in organogenesis in both vertebrates and invertebrates.
Suboptimal expression of T-box genes can result in severe phenotypes. Mice bearing one defective allele of the first recognized T-box protein, Branchyury (T), have shortened-tail phenotypes, whereas homozygous mutants are embryo lethal due to failures in notochord and tailbud development. Mutations in the Tbx6 gene result in abnormal formation of neural tubes in mice. Currently, 12 T-box genes (T, eomes, Tbx1, Tbx2, Tbx3, Tbx4, Tbx5, Tbx6, Tbx14 Tbx15, Tbr-1, and Tbr-2) have been identified in mice.
In humans, hereditary genetic diseases associated with defects in T-box genes have been reported. The ulnar-mammary syndrome is a pleiotropic disorder affecting limb, apocrine gland, tooth, hair, and genital development. This genetic disorder is caused by insufficient expression of Tbx3. The Holt-Oram syndrome, which is characterized by upper-limb malformations and cardiac septation defects, is due to mutations in one of the Tbx5 gene alleles .
A member of the T-box gene family, named Tbt-1, was identified in concanavalin A (ConA)-activated T cells by means of representational differential analysis (RDA) . Tbt-1 is induced in activated Th1 and CD8+ T cells.