title: Vital role of the calpain-calpastatin system for placental-integrity-dependent embryonic survival.
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.
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Takano
authors.forename: Naomi
authors.initials: N
authors.lastname: Mihira
authors.forename: Ryo
authors.initials: R
authors.lastname: Fujioka
authors.forename: Emi
authors.initials: E
authors.lastname: Hosoki
authors.forename: Athar H
authors.initials: AH
authors.lastname: Chishti
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000473:pathology / Q000502:physiology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000473:pathology / Q000502:physiology*; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D020033:Protein Isoforms; C033668:calpastatin; D002154:Calpain