Removing the vertebrate-specific TBP N terminus disrupts placental beta2m-dependent interactions with the maternal immune system.
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, tbp(DeltaN), that produces a version of TBP lacking 111 of the 135 vertebrate-specific amino acids. Most tbp(DeltaN/DeltaN) fetuses (>90%) died in midgestation from an apparent defect in the placenta. tbp(DeltaN/DeltaN) 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 tbp(DeltaN/DeltaN) fetuses increased when fetal/placental beta2m expression was genetically disrupted. These results suggest that the TBP N terminus functions in transcriptional regulation of a placental beta2m-dependent process that favors maternal immunotolerance of pregnancy.
Hobbs
Nicole K
NK
Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59717, USA.
Bondareva
Alla A
AA
Barnett
Sheila
S
Capecchi
Mario R
MR
Schmidt
Edward E
EE
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D019143:Evolution, Molecular; D005260:Female; D005333:Fetus / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D007112:Immunity, Maternally-Acquired / Q000276:immunology*; D007156:Immunologic Memory; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D009154:Mutation; D010920:Placenta / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D011247:Pregnancy; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D004268:DNA-Binding Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D001613:beta 2-Microglobulin