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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\u2010like 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\u2010 or subcellular matrix environment that permits or stimulates cell proliferation. Hopfer, U., Fukai, N., Hopfer, H., Wolf, G., Joyce, N., Li, E., Olsen, B. R. Targeted disruption of\n                    <jats:italic>Col8a1<\/jats:italic>\n                    and\n                    <jats:italic>Col8a2<\/jats:italic>\n                    genes in mice leads to anterior segment abnormalities in the eye. FASEB J. 19, 1232\u20131244 (2005)\n                  <\/jats:p>","DOI":"10.1096\/fj.04-3019com","type":"journal-article","created":{"date-parts":[[2005,7,28]],"date-time":"2005-07-28T19:23:04Z","timestamp":1122578584000},"page":"1232-1244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Targeted disruption of\n                    <i>Col8a1<\/i>\n                    and\n                    <i>Col8a2<\/i>\n                    genes in mice leads to anterior segment abnormalities in the eye"],"prefix":"10.1096","volume":"19","author":[{"given":"Ulrike","family":"Hopfer","sequence":"first","affiliation":[{"name":"Department of Oral and Developmental Biology Harvard School of Dental Medicine  Boston Massachusetts USA"},{"name":"Department of Medicine University of Hamburg  D\u201020246 Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Fukai","sequence":"additional","affiliation":[{"name":"Department of Oral and Developmental Biology Harvard School of Dental Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Hopfer","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Joyce","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Division of Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Novartis Institutes for Biomedical Research  Cambridge MA 02139 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn R.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Oral and Developmental Biology Harvard School of Dental Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,8]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"30","article-title":"EC collagen: biosynthesis by corneal endothelial cells and separation from type IV without pepsin treatment or denaturation","volume":"3","author":"Benya P. 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