Removing the vertebrate-specific TBP N terminus disrupts placental β2m-dependent interactions with the maternal immune system

Abstract

Mammalian TBP consists of a 180 amino acid core that is common to all eukaryotes, fused to a vertebrate-specific N-terminal domain. We generated mice having a modified tbp allele, tbpΔN, that produces a version of TBP lacking 111 of the 135 vertebrate-specific amino acids. Most tbpΔN/ΔN fetuses (>90%) died in midgestation from an apparent defect in the placenta. tbpΔN/ΔN fetuses could be rescued by supplying them with a wild-type tetraploid placenta. Mutants also could be rescued by rearing them in immunocompromised mothers. In immune-competent mothers, survival of tbpΔN/ΔN fetuses increased when fetal/placental β2m expression was genetically disrupted. These results suggest that the TBP N terminus functions in transcriptional regulation of a placental β2m-dependent process that favors maternal immunotolerance of pregnancy.