Abnormal cartilage development and altered N-glycosylation in Tmem165-deficient zebrafish mirrors the phenotypes associated with TMEM165-CDG.
Glycobiology
; 25(6): 669-82, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-25609749
ABSTRACT
The congenital disorders of glycosylation (CDG), a group of inherited diseases characterized by aberrant 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pez Cebra
/
Cartílago
/
Trastornos Congénitos de Glicosilación
/
Modelos Animales de Enfermedad
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Glycobiology
Asunto de la revista:
BIOQUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Bélgica