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About the Authors:
Haruhiko Fujihira
Affiliation: Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, Japan
Yuki Masahara-Negishi
Affiliation: Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, Japan
Masaru Tamura
Affiliation: Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, BioResourse Center, RIKEN, Ibaraki, Japan
Chengcheng Huang
Affiliation: Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, Japan
Yoichiro Harada
Affiliation: Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, Japan
Shigeharu Wakana
Affiliation: Technology and Development Team for Mouse Phenotype Analysis, Japan Mouse Clinic, BioResourse Center, RIKEN, Ibaraki, Japan
Daisuke Takakura
Affiliation: Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan
Nana Kawasaki
Affiliation: Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan
Naoyuki Taniguchi
Affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, Japan
Gen Kondoh
Affiliation: Laboratory of Integrative Biological Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
Tadashi Yamashita
Affiliation: Laboratory of Biochemistry, School of Veterinary Medicine, Azabu University, Kanagawa, Japan
Yoko Funakoshi
Affiliation: Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, Japan
Tadashi Suzuki
* E-mail: [email protected]
Affiliation: Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Saitama, JapanAbstract
The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating enzyme that is highly conserved among eukaryotes. It was recently reported that subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms (NGLY1-deficiency). While the enzyme obviously has a critical role in mammals, its precise function remains unclear. In this study, we analyzed Ngly1-deficient mice and found that they are embryonic lethal in C57BL/6 background. Surprisingly, the additional deletion of the gene encoding endo-[Beta]-N-acetylglucosaminidase (Engase), which is another de-N-glycosylating enzyme but leaves a single GlcNAc at glycosylated Asn residues, resulted in the partial rescue of the lethality of the Ngly1-deficient mice. Additionally, we also found that a change in the genetic background of C57BL/6 mice, produced by crossing the mice with an outbred mouse strain (ICR) could partially rescue...