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Publication : The thyroid hormone receptor-associated protein TRAP220 is required at distinct embryonic stages in placental, cardiac, and hepatic development.

First Author  Landles C Year  2003
Journal  Mol Endocrinol Volume  17
Issue  12 Pages  2418-35
PubMed ID  14500757 Mgi Jnum  J:86857
Mgi Id  MGI:2682174 Doi  10.1210/me.2003-0097
Citation  Landles C, et al. (2003) The Thyroid Hormone Receptor-Associated Protein TRAP220 Is Required at Distinct Embryonic Stages in Placental, Cardiac, and Hepatic Development. Mol Endocrinol 17(12):2418-35
abstractText  Recent work indicates that thyroid hormone receptor-associated protein 220 (TRAP220), a subunit of the multiprotein TRAP coactivator complex, is essential for embryonic survival. We have generated TRAP220 conditional null mice that are hypomorphic and express the gene at reduced levels. In contrast to TRAP220 null mice, which die at embryonic d 11.5 (E11.5), hypomorphic mice survive until E13.5. The reduced expression in hypomorphs results in hepatic necrosis, defects in hematopoiesis, and hypoplasia of the ventricular myocardium, similar to that observed in TRAP220 null embryos at an earlier stage. The embryonic lethality of null embryos at E11.5 is due to placental insufficiency. Tetraploid aggregation assays partially rescues embryonic development until E13.5, when embryonic loss occurs due to hepatic necrosis coupled with poor myocardial development as observed in hypomorphs. These findings demonstrate that, for normal placental function, there is an absolute requirement for TRAP220 in extraembryonic tissues at E11.5, with an additional requirement in embryonic tissues for hepatic and cardiovascular development thereafter.
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