PUBLICATION

Abnormal Cartilage Development and Altered N-Glycosylation in Tmem165-Deficient Zebrafish Mirrors the Phenotypes Associated with TMEM165-CDG

Authors
Bammens, R., Mehta, N., Race, V., Foulquier, F., Jaeken, J., Tiemeyer, M., Steet, R., Matthijs, G., Flanagan-Steet, H.
ID
ZDB-PUB-150123-8
Date
2015
Source
Glycobiology   25(6): 669-82 (Journal)
Registered Authors
Flanagan-Steet, Heather, Steet, Richard
Keywords
N-glycosylation, cartilage, congenital disorders of glycosylation, zebrafish
MeSH Terms
  • Animals
  • Cartilage/growth & development
  • Cartilage/metabolism*
  • Cartilage/pathology*
  • Congenital Disorders of Glycosylation/genetics*
  • Congenital Disorders of Glycosylation/metabolism*
  • Disease Models, Animal*
  • Glycosylation
  • Humans
  • Membrane Proteins/deficiency*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Phenotype
  • Zebrafish/metabolism*
PubMed
25609749 Full text @ Glycobiology
Abstract
The Congenital Disorders of Glycosylation (CDG), a group of inherited diseases characterized by defective glycosylation, encompass a wide range of defects including glycosyltransferases, glycosidases, nucleotide-sugar transporters, as well as proteins involved in maintaining Golgi architecture, pH, and vesicular trafficking. Mutations in a previously undescribed protein, TMEM165, were recently shown to cause a new form of CDG, termed TMEM165-CDG. TMEM165-CDG patients exhibit cartilage and bone dysplasia and altered glycosylation of serum glycoproteins. We utilized a morpholino knockdown strategy in zebrafish to investigate the physiologic and pathogenic functions of TMEM165. Inhibition of tmem165 expression in developing zebrafish embryos caused craniofacial abnormalities, largely attributable to fewer chondrocytes. Decreased expression of several markers of cartilage and bone development suggests that Tmem165 deficiency alters both chondrocyte and osteoblast differentiation. Glycomic analysis of tmem165 morphants also revealed altered initiation, processing, and extension of N-glycans, paralleling some of the glycosylation changes noted in human patients. Collectively, these findings highlight the utility of zebrafish to elucidate pathogenic mechanisms associated with glycosylation disorders and suggest that the cartilage and bone dysplasia manifested in TMEM165-CDG patients may stem from abnormal development of chondrocytes and osteoblasts.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes