Ocular abnormalities in Large(myd) and Large(vls) mice, spontaneous models for muscle, eye, and brain diseases.
Here we demonstrate previously unreported ocular defects in mice homozygous for a new allele of the Large gene, veils, and for Large(myd) mice. Clinically, vitreal fibroplasia and retinal vessel tortuosity and fluorescein leakage are observed. These vascular defects may be due to the extreme disorganization of the astrocytic template on which endothelial cells migrate in the retina. Abnormal electroretinograms recorded from Large(vls) or Large(myd) mice are accompanied by disorganization of the outer plexiform layer (OPL) with a dramatic reduction in the number of synaptic complexes. In both mutants, the internal limiting membrane (ILM) is disrupted with ectopic cells in the vitreous. Interestingly, while all components of the dystrophin glycoprotein complex are present at reduced levels in the OPL, they were absent in the ILM of affected mice. Finally, hypoglycosylation of alpha-dystroglycan previously implicated in muscle and brain defects is also observed in the retina and may contribute to the ocular abnormalities.
Lee
Yongsuk
Y
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Kameya
Shuhei
S
Cox
Gregory A
GA
Hsu
Jennifer
J
Hicks
Wanda
W
Maddatu
Terry P
TP
Smith
Richard S
RS
Naggert
Jürgen K
JK
Peachey
Neal S
NS
Nishina
Patsy M
PM
D000818:Animals; D001483:Base Sequence; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005091:Exons; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005128:Eye Diseases / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*
C502747:Large1 protein, mouse; D017351:N-Acetylglucosaminyltransferases