title: Essential role of synoviolin in embryogenesis.
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.
authors.affiliation: Department of Genome Science, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa 216-8512, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yagishita
authors.forename: Kinuko
authors.initials: K
authors.lastname: Ohneda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Amano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Sugiura
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Tsuchimochi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shin
authors.forename: Ko-Ichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohneda
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohta
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism / Q000502:physiology*; D014965:X-Rays
chemical_list: C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases