Vital Role of the Calpain-calpastatin System for Placental-integrity-dependent Embryonic Survival

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2011 Jul 28

PMID 21791606

Citations 26

Authors

Jiro Takano

Naomi Mihira

Ryo Fujioka

Emi Hosoki

Athar H Chishti

Takaomi C Saido

Affiliations

Soon will be listed here.

Abstract

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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