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Publication : Vital role of the calpain-calpastatin system for placental-integrity-dependent embryonic survival.

First Author  Takano J Year  2011
Journal  Mol Cell Biol Volume  31
Issue  19 Pages  4097-106
PubMed ID  21791606 Mgi Jnum  J:175868
Mgi Id  MGI:5287551 Doi  10.1128/MCB.05189-11
Citation  Takano J, et al. (2011) Vital role of the calpain-calpastatin system for placental-integrity-dependent embryonic survival. Mol Cell Biol 31(19):4097-106
abstractText  Although the calpain-calpastatin system has been implicated in a number of pathological conditions, its normal physiological role remains largely unknown. To investigate the functions of this system, we generated conventional and conditional calpain-2 knockout mice. The conventional calpain-2 knockout embryos died around embryonic day 15, preceded by cell death associated with caspase activation and DNA fragmentation in placental trophoblasts. In contrast, conditional knockout mice in which calpain-2 is expressed in the placenta but not in the fetus were spared. These results suggest that calpain-2 contributes to trophoblast survival via suppression of caspase activation. Double-knockout mice also deficient in calpain-1 and calpastatin resulted in accelerated and rescued embryonic lethality, respectively, suggesting that calpain-1 and -2 at least in part share similar in vivo functions under the control of calpastatin. Triple-knockout mice exhibited early embryonic lethality, a finding consistent with the notion that this protease system is vital for embryonic survival.
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