PUBLICATION
Dolichol-phosphate mannose synthase depletion in zebrafish leads to dystrophic muscle with hypoglycosylated α-dystroglycan
- Authors
- Marchese, M., Pappalardo, A., Baldacci, J., Verri, T., Doccini, S., Cassandrini, D., Bruno, C., Fiorillo, C., Garcia-Gil, M., Bertini, E., Pitto, L., Santorelli, F.M.
- ID
- ZDB-PUB-160614-13
- Date
- 2016
- Source
- Biochemical and Biophysical Research Communications 477(1): 137-43 (Journal)
- Registered Authors
- Keywords
- Congenital muscular dystrophy, Glycosylation, Mannosylation, Zebrafish, α-dystroglycan
- MeSH Terms
-
- Animals
- Dystroglycans/metabolism*
- Female
- Gene Knockdown Techniques
- Glycosylation
- Male
- Mannosyltransferases/classification
- Mannosyltransferases/genetics*
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology*
- Muscular Dystrophies/pathology*
- Phylogeny
- RNA, Messenger/genetics
- Zebrafish/metabolism*
- PubMed
- 27291147 Full text @ Biochem. Biophys. Res. Commun.
Citation
Marchese, M., Pappalardo, A., Baldacci, J., Verri, T., Doccini, S., Cassandrini, D., Bruno, C., Fiorillo, C., Garcia-Gil, M., Bertini, E., Pitto, L., Santorelli, F.M. (2016) Dolichol-phosphate mannose synthase depletion in zebrafish leads to dystrophic muscle with hypoglycosylated α-dystroglycan. Biochemical and Biophysical Research Communications. 477(1):137-43.
Abstract
Defective dolichol-phosphate mannose synthase (DPMS) complex is a rare cause of congenital muscular dystrophy associated with hypoglycosylation of alpha-dystroglycan (α-DG) in skeletal muscle. We used the zebrafish (Danio rerio) to model muscle abnormalities due to defects in the subunits of DPMS. The three zebrafish ortholog subunits (encoded by the dpm1, dpm2 and dpm3 genes, respectively) showed high similarity to the human proteins, and their expression displayed localization in the midbrain/hindbrain area and somites. Antisense morpholino oligonucleotides targeting each subunit were used to transiently deplete the dpm genes. The resulting morphant embryos showed early death, muscle disorganization, low DPMS complex activity, and increased levels of apoptotic nuclei, together with hypoglycosylated α-DG in muscle fibers, thus recapitulating most of the characteristics seen in patients with mutations in DPMS. Our results in zebrafish suggest that DPMS plays a role in stabilizing muscle structures and in apoptotic cell death.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping