Essential Role of Synoviolin in Embryogenesis

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 i...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-03, Vol.280 (9), p.7909-7916
Main Authors: Yagishita, Naoko, Ohneda, Kinuko, Amano, Tetsuya, Yamasaki, Satoshi, Sugiura, Akiko, Tsuchimochi, Kaneyuki, Shin, Hiroshi, Kawahara, Ko-Ichi, Ohneda, Osamu, Ohta, Tomohiko, Tanaka, Sakae, Yamamoto, Masayuki, Maruyama, Ikuro, Nishioka, Kusuki, Fukamizu, Akiyoshi, Nakajima, Toshihiro
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Animals
Apoptosis
Cells, Cultured
Colony-Forming Units Assay
Embryo, Mammalian - metabolism
Embryo, Mammalian - physiology
Endoplasmic Reticulum - metabolism
Female
Fibroblasts - metabolism
Gene Expression Regulation, Developmental
Immunohistochemistry
Mice
Mice, Inbred DBA
Mice, Transgenic
Models, Biological
Mutation
Phenotype
Time Factors
Ubiquitin-Protein Ligases - metabolism
Ubiquitin-Protein Ligases - physiology
X-Rays
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M410863200