PUBLICATION

Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos

Authors

Parsons, M.J., Campos, I., Hirst, E.M.A., and Stemple, D.L.

ID

ZDB-PUB-020708-4

Date

2002

Source

Development (Cambridge, England) 129(14): 3505-3512 (Journal)

Registered Authors

Parsons, Michael, Stemple, Derek L.

Keywords

dystroglycan; muscular dystrophy; dystrophin; zebrafish; Danio rerio; sarcomere; sarcoplasmic reticulum

MeSH Terms

Animals
Base Sequence
Central Nervous System/embryology
Cytoskeletal Proteins/genetics
Cytoskeletal Proteins/physiology*
Dystroglycans
Gene Expression Regulation, Developmental
Gene Targeting
Humans
In Situ Hybridization
Laminin/metabolism
Membrane Glycoproteins/genetics
Membrane Glycoproteins/physiology*
Mice
Muscle, Skeletal/embryology
Muscular Dystrophy, Animal/etiology*
Muscular Dystrophy, Animal/genetics
Neuromuscular Junction/embryology
Oligodeoxyribonucleotides, Antisense/genetics
Oligodeoxyribonucleotides, Antisense/pharmacology
Zebrafish/embryology*
Zebrafish/genetics

(all 22)

PubMed

12091319 Full text @ Development

Abstract

Muscular dystrophy is frequently caused by disruption of the dystrophin- glycoprotein complex (DGC), which links muscle cells to the extracellular matrix. Dystroglycan, a central component of the DGC, serves as a laminin receptor via its extracellular alpha subunit, and interacts with dystrophin (and thus the actin cytoskeleton) through its integral membrane beta subunit. We have removed the function of dystroglycan in zebrafish embryos. In contrast to mouse, where dystroglycan mutations lead to peri-implantation lethality, dystroglycan is dispensable for basement membrane formation during early zebrafish development. At later stages, however, loss of dystroglycan leads to a disruption of the DGC, concurrent with loss of muscle integrity and necrosis. In addition, we find that loss of the DGC leads to loss of sarcomere and sarcoplasmic reticulum organisation. The DGC is required for long-term survival of muscle cells in zebrafish, but is dispensable for muscle formation. Dystroglycan or the DGC is also required for normal sarcomere and sarcoplasmic reticulum organisation. Because zebrafish embryos lacking dystroglycan share several characteristics with human muscular dystrophy, they should serve as a useful model for the disease. In addition, knowing the dystroglycan null phenotype in zebrafish will facilitate the isolation of other molecules involved in muscular dystrophy pathogenesis.

Genes / Markers

Marker	Marker Type	Name
dag1	GENE	dystroglycan 1
dmd	GENE	dystrophin
lamc1	GENE	laminin, gamma 1
z21243	SSLP	Z21243

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-dag1	standard conditions	Prim-5	muscle disorganized, abnormal	Fig. 4
WT + MO1-dag1	standard conditions	Prim-5	muscle necrotic, abnormal	Fig. 4
WT + MO1-dag1	standard conditions	Prim-5	muscle sarcomere decreased amount, abnormal	Fig. 4
WT + MO1-dag1	standard conditions	Prim-5	muscle sarcomere morphology, abnormal	Fig. 4
WT + MO1-dag1	standard conditions	Prim-5	muscle sarcoplasmic reticulum unstructured, abnormal	Fig. 4
WT + MO1-dag1	standard conditions	Prim-5	musculoskeletal movement disrupted, abnormal	Fig. 2
WT + MO1-dag1	standard conditions	Prim-5	post-vent region increased curvature, abnormal	Fig. 2
WT + MO1-dag1	standard conditions	Prim-5	whole organism dystrophic, abnormal	Fig. 2
WT + MO1-dag1	standard conditions	Long-pec	central nervous system structure, normal	Fig. 5
WT + MO1-dag1	standard conditions	Long-pec	embryo development delayed, abnormal	Fig. 2

1 - 10 of 14

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
lamc1_unspecified		Unspecified	lamc1

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
dag1	MO1-dag1	MRPHLNO

Fish

Fish
lamc1^{unspecified/unspecified}
WT
WT + MO1-dag1

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Parsons et al., 2002 ZDB-PUB-020708-4 PMID:12091319

Removal of dystroglycan causes severe muscular dystrophy in zebrafish embryos

Parsons et al., 2002

ZDB-PUB-020708-4
PMID:12091319