Removing the Vertebrate-Specific TBP N Terminus Disrupts Placental β2m-Dependent Interactions with the Maternal Immune System

Nicole K Hobbs; Alla A Bondareva; Sheila Barnett; Mario R Capecchi; Edward E Schmidt

doi:10.1016/S0092-8674(02)00806-1

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Removing the Vertebrate-Specific TBP N Terminus Disrupts Placental β2m-Dependent Interactions with the Maternal Immune System

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Removing the Vertebrate-Specific TBP N Terminus Disrupts Placental β2m-Dependent Interactions with the Maternal Immune System

Nicole K Hobbs, Alla A Bondareva, Sheila Barnett, Mario R Capecchi and Edward E Schmidt

Cell (Cambridge), Vol.110(1), pp.43-54

2002

DOI: https://doi.org/10.1016/S0092-8674(02)00806-1

Handle:

https://hdl.handle.net/2376/110339

PMCID: PMC2701386

PMID: 12150996

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https://doi.org/10.1016/S0092-8674(02)00806-1View

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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, tbp ΔN , that produces a version of TBP lacking 111 of the 135 vertebrate-specific amino acids. Most tbp ΔN/ΔN fetuses (>90%) died in midgestation from an apparent defect in the placenta. tbp ΔN/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 tbp ΔN/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.

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Title: Removing the Vertebrate-Specific TBP N Terminus Disrupts Placental β2m-Dependent Interactions with the Maternal Immune System
Creators: Nicole K Hobbs - Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59717 USA
Alla A Bondareva - Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59717 USA
Sheila Barnett - Howard Hughes Medical Institute, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112 USA
Mario R Capecchi - Howard Hughes Medical Institute, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112 USA
Edward E Schmidt - Veterinary Molecular Biology, Marsh Laboratories, Montana State University, Bozeman, MT 59717 USA
Publication Details: Cell (Cambridge), Vol.110(1), pp.43-54
Academic Unit: UNKNOWN
Publisher: Elsevier Inc
Identifiers: 99900547053901842
Language: English
Resource Type: Journal article