Removing the vertebrate-specific TBP N terminus disrupts placental beta2m-dependent interactions with the maternal immune system

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Oncological Sciences; Biology; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Capecchi, Mario R.
Other Author Hobbs, Nicole K.; Bondareva, Alla A.; Barnett, Sheila; Schmidt, Edward E.
Title Removing the vertebrate-specific TBP N terminus disrupts placental beta2m-dependent interactions with the maternal immune system
Date 2002-07-12
Description 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.
Type Text
Publisher Cell Press
Journal Title Cell
Volume 110
Issue 1
First Page 43
Last Page 54
Subject Alleles; Animals, Genetically Modified; Binding Sites; Embryonic and Fetal Development; Evolution, Molecular; Female; Fetus; Immune Tolerance; Male; Mice; Mutation; ATA-Box Binding Protein
Subject MESH DNA-Binding Proteins; Immunity, Maternally-Acquired; Maternal-Fetal Exchange; Placenta; Transcription Factors; beta 2-Microglobulin
Language eng
Bibliographic Citation Cell. 2002 Jul 12;110(1):43-54. Hobbs NK, Bondareva AA, Barnett S, Capecchi MR, Schmidt EE. Removing the vertebrate-specific TBP N terminus disrupts placental beta2m-dependent interactions with the maternal immune system. Retrieved on November 2, 2006 from http://linkinghub.elsevier.com/retrieve/pii/S0092867402008061.
Rights Management Copyright © 2002 Cell Press. All rights reserved.
Format Medium application/pdf
Identifier ir-main,565
ARK ark:/87278/s63j3x25
Setname ir_uspace
ID 702671
Reference URL https://collections.lib.utah.edu/ark:/87278/s63j3x25