Mid-and late-gestation lethality in mice lacking the N terminus of TATA-binding protein
Hobbs, Nicole Kay.
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TATA-binding protein (TBP) is a transcription factor comprised of a 180 amino acid core that is shared by all eukaryotes. TBP also has an N-terminal region that, in vertebrates, is highly conserved. We have generated mice bearing a mutant tbp allele, tbp deltaN, that lacks 111 of the 135 amino acids of the vertebrate-specific N terminus. Most homozygous mutants, tbp deltaN/deltaN, die at midgestation from an apparent defect in their placentas. tbp deltaN/deltaN fetuses were rescued at this midgestational crisis if supplied with a wild-type tetraploid placenta. tbp deltaN/deltaN fetuses also survived in immune-normal mothers when fetal/placental beta 2m expression was genetically disrupted. When reared in immunocompromised mothers, tbp deltaN/deltaN fetuses also survived midgestation. These results suggest the N terminus of TBP functions in beta 2M-dependent processes and within the placenta to favor immunotolerance during pregnancy at midgestion. Beyond midgestation, tbp deltaN/deltaN fetuses that survive in immunocompromised mothers were found to be runted at the perinatal period and died shortly after birth. These latter results suggest that the N terminus of TBP also functions in non-immune processes required for normal birth weight and successful pregnancy.