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Abstract #24298 Published in IGR 11-3
Developmental distribution of collagen IV isoforms and relevance to ocular diseases
Bai X; Dilworth DJ; Weng Y-C; Gould DBMatrix Biology 2009; 28: 194-201
Type IV collagens are the most abundant proteins in basement membranes. Distinct genes encode each of six isoforms, α1(IV) through α6(IV), which assemble into one of three characteristic heterotrimers. Disease-causing mutations in each of the six genes are identified in humans or mice and frequently include diverse ocular pathogenesis that encompass common congenital and progressive blinding diseases, such as optic nerve hypoplasia, glaucoma, and retinal degeneration. Understanding where and when collagen IV molecules are expressed is important because it defines limits for the location and timing of primary pathogenesis. Although localization of collagen IV isoforms in developed human eyes is known, the spatial and temporal distribution of type IV collagens throughout ocular development has not been determined in humans or in mice. Here, we use isoform-specific monoclonal antibodies to systematically reveal the localization of all six collagen IV isoforms in developing mouse eyes. We found that α1(IV) and α2(IV) always co-localized and were ubiquitously expressed throughout development. α3(IV) and α4(IV) also always co-localized but in a much more spatially and temporally specific manner than α1(IV) and α2(IV). α5(IV) co-localized both with α3(IV)/α4(IV), and with α6(IV), consistent with α5(IV) involvement in two distinct heterotrimers. α5(IV) was present in all basement membranes except those of the vasculature. α6(IV) was not detected in vasculature or in Bruch's membrane, indicating that α5(IV) in Bruch's membrane is part of the α3α4α5 heterotrimer. This comprehensive analysis defines the spatial and temporal distribution of type IV collagen isoforms in the developing eye, and will contribute to understanding the mechanisms underlying collagen IV-related ocular diseases that collectively lead to blindness in millions of people worldwide.
Dr. D.B. Gould, Departments of Ophthalmology and Anatomy, Institute of Human Genetics, University of California, San Francisco, CA 94143, USA. gouldd@vision.ucsf.edu
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)