Essential role of Synoviolin in embryogenesis

Naoko Yagishita, Kinuko Ohneda, Tetsuya Amano, Satoshi Yamasaki, Akiko Sugiura, Kaneyuki Tsuchimochi, Hiroshi Shin, Ko Ichi Kawahara, Osamu Ohneda, Tomohiko Ohta, Sakae Tanaka, Masayuki Yamamoto, Ikuro Maruyama, Kusuki Nishioka, Akiyoshi Fukamizu, Toshihiro Nakajima

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

We recently reported the importance of Synoviolin in quality control of proteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) system and its involvement in the pathogenesis of arthropathy through its anti-apoptotic effect. For further understanding of the role of Synoviolin in vivo, we generated in this study synoviolin-deficient (syno-/-) mice by genetargeted disruption. Strikingly, all fetuses lacking syno died in utero around embryonic day 13.5, although Hrd1p, a yeast orthologue of Synoviolin, is non-essential for survival. Histologically, hypocellularity and aberrant apoptosis were noted in the syno-/- fetal liver. Moreover, definitive erythropoiesis was affected in non-cell autonomous manner in syno-/- embryos, causing death in utero. Cultured embryonic fibroblasts derived from syno-/- mice were more susceptible to endoplasmic reticulum stress-induced apoptosis than those from syno+/+ mice, but the susceptibility was rescued by overexpression of synoviolin. Our findings emphasized the indispensable role of the Synoviolin in embryogenesis.

Original languageEnglish
Pages (from-to)7909-7916
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number9
DOIs
Publication statusPublished - 2005 Mar 4
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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