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

D ow nloaded from 2 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