Targeted disruption of Col8a1 and Col8a2 genes in mice leads to anterior segment abnormalities in the eye.
Collagen VIII is localized in subendothelial and subepithelial extracellular matrices. It is a major component of Descemet's membrane, a thick basement membrane under the corneal endothelium, where it forms a hexagonal lattice structure; a similar structure, albeit less extensive, may be formed in other basement membranes. We have examined the function of collagen VIII in mice by targeted inactivation of the genes encoding the two polypeptide subunits, Col8a1 and Col8a2. Analysis of these mice reveals no major structural defects in most organs, but demonstrates that type VIII collagen is required for normal anterior eye development, particularly the formation of a corneal stroma with the appropriate number of fibroblastic cell layers and Descemet's membrane of appropriate thickness. Complete lack of type VIII collagen leads to dysgenesis of the anterior segment of the eye: a globoid, keratoglobus-like protrusion of the anterior chamber with a thin corneal stroma. Descemet's membrane is markedly thinned. The corneal endothelial cells are enlarged and reduced in number, and show a decreased ability to proliferate in response to different growth factors in vitro. An important function of collagen VIII may therefore be to generate a peri- or subcellular matrix environment that permits or stimulates cell proliferation.
Hopfer
Ulrike
U
Department of Oral and Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Fukai
Naomi
N
Hopfer
Helmut
H
Wolf
Gunter
G
Joyce
Nancy
N
Li
En
E
Olsen
Bjorn R
BR
D000818:Animals; D000869:Anterior Eye Segment / Q000002:abnormalities* / Q000196:embryology; D001011:Aorta / Q000378:metabolism; D049109:Cell Proliferation; D024102:Collagen Type VIII / Q000235:genetics / Q000502:physiology*; D003315:Cornea / Q000648:ultrastructure; D004728:Endothelium, Corneal / Q000473:pathology; D005124:Eye Abnormalities / Q000209:etiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
C507463:Col8a2 protein, mouse; D024102:Collagen Type VIII