Mid-and late-gestation lethality in mice lacking the N terminus of TATA-binding protein

by Hobbs, Nicole Kay.

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?N, that lacks 111 of the 135 amino acids of the vertebratespecifi c N terminus. Most homozygous mutants, tbp?N/? N/?N, die at midgestation from an apparent defect in their placentas. tbp?N/? N/?N fetuses were rescued at this midgestational crisis if supplied with a wild-type tetraploid placenta. tbp?N/? N/? fetuses also survived in immune-normal mothers when fetal/placental ? 2 m expression was genetically disrupted. When reared in immunocompromised mothers, tbp?N/? N/?N fetuses also survived midgestation. These results suggest the N terminus of TBP functions in ? 2 M-dependent processes and within the placenta to favor immunotolerance during pregnancy at midgestion. Beyond midgestation, tbp?N/? N/?N 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. N/ N 1