ZFIN ID: ZDB-PUB-110921-31
Abnormal Vascular Development in Zebrafish Models for Fukutin and FKRP Deficiency
Wood, A.J., Müller, J.S., Jepson, C.D., Laval, S.H., Lochmüller, H., Bushby, K., Barresi, R., and Straub, V.
Date: 2011
Source: Human molecular genetics   20(24): 4879-90 (Journal)
Registered Authors: Wood, Alasdair
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Antibodies/immunology
  • Blood Vessels/abnormalities*
  • Blood Vessels/drug effects
  • Blood Vessels/embryology*
  • Blood Vessels/pathology
  • Dystroglycans/metabolism
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology
  • Eye/blood supply
  • Eye/drug effects
  • Eye/pathology
  • Glycosyltransferases/deficiency*
  • Glycosyltransferases/metabolism
  • Models, Animal
  • Morpholinos/pharmacology
  • Phalloidine/metabolism
  • Proto-Oncogene Protein c-fli-1
  • Somites/abnormalities
  • Somites/blood supply
  • Somites/drug effects
  • Somites/embryology
  • Staining and Labeling
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/metabolism
PubMed: 21926082 Full text @ Hum. Mol. Genet.

Fukutin and fukutin-related protein (FKRP) are involved in the glycosylation of α-dystroglycan, a key receptor for basement membrane proteins. Aberrant α-dystroglycan glycosylation leads to a broad spectrum of disorders, ranging from limb-girdle muscular dystrophy to Walker-Warburg Syndrome. This is the first study investigating a role for fukutin and FKRP mediated glycosylation in angiogenesis. Transgenic zebrafish expressing enhanced green fluorescent protein in blood vessels were treated with morpholino antisense oligonucleotides that blocked the expression of fukutin, FKRP and dystroglycan. All morphant fish showed muscle damage and vascular abnormalities at 1 day post fertilisation. The intersegmental vessels of somites failed to reach the dorsal longitudinal anastomosis and in more severe phenotypes retracted further or were in some cases even completely missing. In contrast, the eye vasculature was distorted in both fukutin and FKRP morphants, but not in dystroglycan morphants or control fish. The eye size was also smaller in the fukutin and FKRP morphants as compared to dystroglycan knock down fish and controls. In general the fukutin morphant fish had the most severe skeletal muscle and eye phenotype. Our findings suggest that fukutin and FKRP have functions that affect ocular development in zebrafish independently of dystroglycan.

Despite anecdotal reports about vascular abnormalities in patients affected by dystroglycanopathies, the clinical relevance of such lesions remains unclear and should be subject to further review and investigations.